text:
A Comparative Study of Split-Root and Bone Removal in the Extraction of Mandibular Impacted Third Molars
Wen-chao Li*, Ning Ruan, Guang-hui Lv, Yang Lin, Min-qiang Zhao, Bo-chen Lei, Yi-fu Wang, Wei Zu, Yuan Tian
Department of Oral Surgery, Affiliated Hospital of Chifeng College, Chifeng, China
To cite this article:
Wen-chao Li, Ning Ruan, Guang-hui Lv, Yang Lin, Min-qiang Zhao, Bo-chen Lei, Yi-fu Wang, Wei Zu, Yuan Tian. A Comparative Study of Split-Root and Bone Removal in the Extraction of Mandibular Impacted Third Molars. Journal of Surgery. Vol. 4, No. 2, 2016, pp. 8-12. doi: 10.11648/j.js.20160402.11
Abstract: This paper is aimed to compare the effects of split-root procedures and bone removal procedures in the extraction of mandibular medial vertical impacted third molars. This was a prospective study conducted at the Department of Oral Surgery of theChifeng College Affiliated Hospital on consecutive patients between January 2015 and December 2015. The study result showed that the operative time of the split-root group was shorter, and the dental root fracture was less than the bone removal group. This study suggested that the short-term outcomes of medial vertical impacted third molar operations (facial swelling, pain and mouth opening) differed depending on the surgical approach.
Keywords: Split-Root, Bone Removal, Vertical Impacted Teeth, Third Molar
In early 1966, Archer  defined an impacted third molars (ITMs) because of malposition or lack of space is prevented from erupting into position. Along with the jaw degradation, more and more ITMs were found in the clinical examination.
The most popular are Winter’s  and Pell and Gregory’s  systems which classify the height of the mandible ITMs, the angulation of the second molar, the occlusal plane and the ascending mandibular ramus.
According to Samira  and Ahu , the ITMs incidence is 54.3% and 54.1% of young adults in Saudi and Turkish. The ITMs incidence is up to 68.6% of the Chinese population in Singapore .Kruger  and Yuasa  had claimed that the incidence of mandibular ITMs are higher in females. Mandibular medial vertical ITMs are one of the ITMs classifications. Some studies have reported that the incidence of mandibular vertical ITMs accounted for 43.8% of the mandibular ITMs in China .
The extraction of mandibular ITMs is one of the most frequently performed procedures in oral surgery [3,7,10]. Generally, most of the surgeries are performed under local anesthesia in dental clinics [3,8,11]. The surgical removal of mandibular ITMs generally produces facial swelling, pain, and limited mouth opening , which affects the quality of life and restricts daily activities of the patient in the short term . There are many factors that influence the postoperative outcome, but surgical procedure is one of the reasons behind this [11, 13, 14, 15, 16, 17]. Many oral and maxillofacial surgeons have therefore put stress on better facial swelling, pain, and trismus control in patients who undergo ITMs extractions .
The extraction of mandibular vertical ITMs can be used on the bone removal procedures, and can also be used on the split-root procedures. Currently, there has not been a reported comparison on the dentalrootfracture, operative time and postoperative complications between the split-root procedures and the bone removal procedures in mandibular vertical ITMs extraction surgery.
The purpose of this study was to compare the differences of dental root fracture, operative time and possible postoperative complications between the split-root procedures and the bone removal procedures in mandibular vertical ITMs extractionsurgeries, and to evaluate the advantages and disadvantages of the two procedures. This study will provide the best surgical procedure in mandibular vertical ITMs extraction surgery.
2. Material and Methods
The present study received approval from the local Ethics Committee. The subjects were selected from a pool of patients admitted for Oral Surgery treatment between January 2015 and December 2015. A prospective study was implemented involving 30 healthy patients between 21 and 40 years old. All patients signed a statement of informed consent.
• Male patients were scheduled for a bilateral surgical removal of symmetrically placed mandibularITMs and without systemic disease.
• The ITMs had multiple dental rootsin panoramic films.
• Panoramic radiographs were taken to ensure the similarity of the ITMsbased on Winter’s classification (only vertical positions were used) and the Pell & Gregory classification (only classⅡ-B were used) [2, 3].
• No any contraindications for oral surgery, no pericoronitis, and were not taking any medication long-term.
Thirty patients (60 mandibular vertical ITMs) were treated with autologous about control, and were randomly assigned to the experimental group or the control group. The experimental group received split-root procedures and the control group received bone removal procedures. A coin toss determined the surgery sequence procedure. The surgery interval was 3 weeks. Thedental root fracture, operative time, facial swelling, pain and mouth opening were recorded.
Preoperatively, all patients orally took 150 mg of Roxithromycin release capsules 30 minutes prior to surgery and used 10 ml of 0.02% chlorhexidine for 2 min. The same oral surgeon operated on each patient. A 1.0% povidone-iodine solution and a 0.02% chlorhexidine rinse were applied to the extra-oral and intra-oral antisepsis. The alveolar, lingual and long buccal nerve block technique was used for achieving effective anaethesia with 2.0% lidocaine with 1:200,000 epinephrine at the site of the surgery. The gums were given an "1" shaped incision and the mucoperiosteal flap was raised. When the Split-root group first with 45° elevation turbines along the long axis of the ITMs cutting the mesial dental root and distal dental root apart. Then the mesial dental root was removed, and finally, the distal dental root was removed with the elevator. Thebone removal group first with 45° elevation turbines to remove the distal bone of the ITMs, then extract the third molars with elevator or dental pliers. All procedures were performed under constant irrigation with saline. Socket was cleaned after the tooth was removed. The 4-0 absorbable suture was used for hermetically suturing the mucoperiosteal flap. One vertical ITMs was removed on the first surgical visit and the contralateral vertical ITMs was removed two weeks later.
Post operative instructions included the following.
• Apply ice pack for 6 hrs after surgery. Practice a soft diet for 3 days. Strenuous exercise is prohibited for 3 days.
• 0.02% Chlorhexidine mouth rinse for one minute thrice daily after diet. Roxithromycin release capsules 150 mg. Ornidazole 500 mg, twice a day for 3 days. Ibuprofen Modify-release Capsules were also used as the rescue drug.
• Patients referral on 48 and 120 hrs after surgery.
Evaluation Criteria: The following variables were recorded.
The operation time was recorded from the start of the cutting of the gums at the site of the ITMs, until the suture at the surgical site was completed with a stopwatch.
Dental root fracture:
No dental root fracture wasrecorded 0, breaking one dental root was recorded 1, breaking two dental roots were recorded 2, and so on. If necessary, shoot apical film examination.
Pain (VAS score):
A 10-level visual analog scale (VAS) was used for assessing patients’ pain intensity (Fig. 1). The scale indicates an intensity range from no pain (0) to worst pain (10) [15,19]. On the 48th and 120th hours after surgery, the pain rating was evaluated. The patients were authorized to take analgesics (Ibuprofen Modify-release Capsules 300 mg twice a day) in case of pain on the first day after surgery. The amount of the analgesia was recorded.
Facial swelling was measured by using facial following lines. The first line corresponded to the horizontal line (AB) joined from the tragus point (A) to the ipsilateral altercation point (B). Another vertical line (CD) was joinedfrom the ipsilateral outer canthus point (C) of the eye to the mandibular angle point (D) (Fig. 2). It was measured with a thread and was then transferred on scale [15,20]. The average data of the differences from the postoperative and preoperative values was calculated.
Facial measurements were taken both before surgery and on the 48th and 120th hour after surgery. Before surgery and postoperatively on the 48 and 120 hrs take the facial measurement. The average data of the differences from the postoperative and preoperative values was calculated.
Mouth opening was assessed by measuring the maximal interincisal distance (MID) both before surgery, and on the 48th and 120th hours aftersurgery. (Fig. 3). The average data of the differences from the postoperative and preoperative values was calculated.
In order to avoid observer bias, all data was recorded by the same independent blinded investigator. The Statistical Package for Social Sciences (SPSS) 16.0 for Windows was used for analyzing and calculating data. The differences of mean operative time, root fracture, facial swelling, pain and trismus in the split-root group and bone removal group were analyzed using the paired samples T-test. A probability of less than 0.05 was considered significant for all tests.
There was a total of 60 ITMs of the 30 male patients in the present study. [Mean age ± standard deviation: 25.86 ± 3.11 years (range: 21 to 40 years). However, 4 cases of bone removal group because removal difficult to split-root procedure.
The statistical analysis revealed that the mean operative time of the split-root group was shorter than the bone removal group; there was a significant difference between the two groups (P＜0.05). There were 5 cases of the dental root fracture in the split-root group, while the bone removal grouped yielded 13 cases. There was a significant difference between the two groups (P＜0.05).(Table 1). The dental root fracture of split-root group was 5 cases and the bone removal group was 13 cases, there was significant difference between the two groups (P＜0.05).(Table 1).
|Groups||Cases||Operative time(min)||Dental root fracture|
|Split-root group||30||6.12 ± 2.14||0.1 ± 0.24|
|Bone removal group||30||8.34 ± 3.56||0.26 ± 0.64|
The pain, facial swelling, and limited mouth opening of the split-root group was less severe than that of the bone removal group; the mean differences were significant (P=0.01, P=0.00 and P=0.00 respectively) on the 48 hours. After 120 hours, there was no significant difference of pain and facial swelling between the two groups. There was however a statistically significant difference (P＜0.05) between the two groups on the 120th hour postoperatively, with the subjects in the bone removal group showing a smaller mouth opening when compared to the split-root group. (Table 2, Table 3 and Table 4).
|Groups||Cases||48 hours after surgery||120 hours after surgery|
|Split-root group||30||2.42 ± 2.54||0.22 ± 0.34|
|Bone removal group||30||4.14 ± 2.76||0.28 ± 0.32|
|Group||Cases||48 hours after surgery||120 hours after surgery|
|The difference of AB||The Difference of CD||The difference of AB||The difference of CD|
|Split-root group||30||0.86 ± 0.51||0.95 ± 0.46||0.20 ± 0.12||0.25 ± 0.16|
|Bone removal group||30||1.38 ± 0.62||1.24 ± 0.55||0.25 ± 0.20||0.28 ± 0.22|
|Groups||Cases||48 hours after surgery||120 hours after surgery|
|Split-root group||30||2.25 ± 1.04||0.41 ± 0.44|
|Bone removal group||30||4.54 ± 1.16||0.78 ± 0.52|
The amount of Oral Ibuprofen Modify-release Capsules postoperatively in patients of the split-root group was less than that of the bone removal group; the mean difference was significant (P＜0.05) (Table 5).
|Groups||Cases||Oral Ibuprofen Modify-release Capsules (grams)|
|Split-root group||30||0.45 ± 0.44|
|Bone removal group||30||0.80 ± 0.73|
Themandibular ITMs are one of the most common oral surgery diseases . The ITMs often cause pericoronitis, periodontitis, cysts or neoplasms, periapical abscess, and resorption of adjacent roots . Thus, most ITMs need to be removed .
The surgical removal of mandibular ITMs generally produces facial swelling, pain and a limited mouth opening . There are many factors that influence the postoperative outcome (such as patient age, gender, weight and dental factors) [8,19,21,22,23,24]. In order to reduce the impact of many factors of surgical complications in the extraction of ITMs, the inclusion criteria of these cases were male patients between 21 and 40 years old [mean age ± standard deviation: 25.86 ± 3.11] scheduled for the bilateral surgical removal of symmetrically placed mandibular ITMs, similar weight, no ethnic differences, no pericoronitis and were not taking any medicationlong-term inthe present study. All data was recorded by the same independent blinded investigator. The methodology used in the present study was more specific to avoid bias and to improve the reliability of the results.
Some studies have reported that the incidence of mandibular vertical ITMs accounted for 43.8% of the mandibular ITMs in China . We found that the removal of mandibular vertical ITMs with multiple dental roots can use the bone removalprocedure and/or the split-root procedure. The principles of the two procedures are different. Bone removalprocedure first with turbines to remove the distal bone of ITMs, then extract the third molars with elevator or dental pliers. However,split-rootprocedure first with turbines cutting tooth to themesial dental root and distal dental root apart,the mesial dental root lose distal resistance, then remove the mesial dental root. Concurrently, the distal dental root lose mesial resistance, and finally remove the distal dental root with elevator or dental pliers. According to clinical observations, the surgical trauma,dental root fracture and postoperative complications of the split-rootprocedurewere less than the bone removal procedure. The results ofthe present study are consistent with the clinical observations, which is in agreement with the findings reported by Ren-yi SUN .
The operative time and dental root fracture of the split-root procedure were less than the bone removal procedure in the present study, which related to the surgical accidents . When extracted mandibular medial vertical ITMs applied the bone removal procedure, the operative time was shorter if the dental root had a small furcation. Reversely, the operative time was longer if the dental root had a big furcation. At the same time, the bone removal increased surgical trauma in addition. While the effect of dental root furcation in the split-root procedure was less than bone removal procedure. Therefore, the operation time of the split-root procedure was short.
The pain, facial swelling, limited mouth opening and Oral Ibuprofen Modify- release Capsules of the split-root group was less severe than that of the bone removal groupon the 48th hour postoperatively. This finding may be attributed to secondary postoperative hypersensitivity , which may be related to the longer operation time and surgical trauma [10, 13, 14, 15, 22, 25]. After 120 hours, there was no significant difference of pain and facial swelling between the two groups. However, the bone removal group showed a smaller mouth opening compared to the split-root group, which may be related to the longer operation time, surgical trauma and jemporomandibular joint damage [10, 15, 19]. However, this issue needs to be investigated in further studies. In the present study, 8 cases of jemporomandibular joint damage were observed in the bone removal group, while only 2 cases of jemporomandibular joint damage were observed in the split-root group, which may be related to the larger force of using the elevator. After a reasonable treatment, 10 patients recovered after two weeks.
Although the postoperative complications of the split-root procedurewere less severe than that of the bone removal procedure, there are limitations in the split-root procedure. First, the split-root procedure is difficult if the dental root has a small and low furcation. It will be increased the surgery difficulty if the split-root fails. Second, the split-root procedure requires a long bur (25mm), which is easy to damage the bone below the dental root furcation and the bone both sides of ITMs. This procedure required oral and maxillofacial surgeons to accurately determine the location of the alveolar bone. Finally, the mouth opening of patients was larger in the split-root group than the bone removal group .
According to the author's clinical experience, the bone removal procedure should be used if the dental root of the mandibular medial vertical ITMs has a small and low furcation. This method can improve the operation efficiency. The split-root procedure should be used if the dental root has a big furcation. This procedure can reduce surgical trauma and the difficulty of surgery operation.
Based on the findings of the present study, the operative time of the split-root procedure is shorter. The dental root fracture and postoperative complications of the split-root procedure were less common in the extraction of mandibular medial vertical ITMs with multiple dental roots. The short-term outcomes of medial vertical impacted third molar operations (facial swelling, pain and mouth opening) differed depending on the surgical approach. However, due to the limitation of the present study, the results should be interpreted with caution. Further studies should be carried out by associations between operation time and jemporomandibular joint damage of mandibular ITMs extractions.
This study was supported by Stomatological Association of Inner Mongolia (IMSA-2015-C6).


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A few months ago, I wrote an article for the World Economic Forum called “A Yellow Card for the Global Economy.” I intended it to serve as a warning about the rising imbalances of the emerging and leading economies. Unfortunately, since then, those imbalances have continued to rise and market complacency has reached new highs.
Last week, financial markets were dyed red, and the stock market reaction added to concerns about a possible impending recession.
The first thing we must understand is that we are not facing a panic created by an economic black swan, but rather by factors that few could deny are evident:
- Excessive valuations, as $20 trillion of monetary stimulus have inflated most financial assets
- Bond yields rising as the U.S. 10-year yield reaches 3.2 percent
- The yuan devaluation, which is on its way to surpass 7 yuan per U.S. dollar
- Global growth estimates trimmed for the sixth time in as many months
Therefore, the U.S. rate hikes—announced repeatedly and incessantly for years—are not the cause; neither is the alleged trade war. These are just symptoms, excuses to disguise a much more worrying illness.
We are experiencing the saturation of excesses built around central banks’ loose policies and the famous “everything bubble.” Therein lies the problem.
After $20 trillion of reckless monetary expansion, risk assets—from the safest to the most volatile and from the most liquid to the unquoted—have skyrocketed without the anchor of sustainable value creation.
In Europe, no investor would buy bonds of eurozone countries with these low yields and high risks in a normal environment.
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With more than $6.5 trillion in bonds with a negative yield, the global bubble remains huge. Stock markets are on fire, valuation multiples soaring, and junk bonds at the lowest yields in 35 years.
And last week, we saw the first signs of trouble in the markets since early February.
China in Trouble
China reminded us that the tale of synchronized growth was false and that what we have been seeing in recent years has been synchronized growth of debt.
When China devalues the yuan and introduces the biggest tax cut in 38 years and a constant monetary stimulus to bail out its banks, what is it really telling us? That everything is fine? No, that things are not going well with the Asian giant.
No economy launches a massive undercover bailout of the financial sector, cuts rates, implements huge tax cuts, and devalues the currency if everything is going smoothly.
The realization of the fallacy of synchronized growth has also brought down expectations of global growth—and with it, corporate profit estimates.
Markets, suddenly, look as expensive as many have warned when the combination of China devaluation and soaring U.S. yields show the extent of the accumulation of risk of the past years.
The cracks in the building always appear first with currencies. Countries that have become accustomed to the idea that “this time is different,” and that debt does not matter, have started to multiply their indebtedness in foreign currency.
In the first three months of 2018, global debt rose 11 percent to a record of $247 trillion, according to the Institute of International Finance, and that of emerging markets soared by $2.5 trillion to an all-time high of $58.5 trillion.
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Markets woke up to a reality that we had decided to ignore: Rates do rise, making it harder to refinance, and finance in the first place.
And if the safest bond gives a return of 3.2 percent, am I willing to buy bonds from much riskier countries with negligible spreads?
The inevitable devaluation of the yuan, which soared to almost seven per dollar, a magical line in the sand which the Chinese regime had never let it cross before.
Am I willing to buy emerging markets and commodities when China exports its imbalances sending disinflationary pressure to the rest of the world?
The U.S. 10-year shows us the risk in the assets that we perceive as “safe.” The yuan reminds us that China exports global disinflation and warns of impossible growth expectations.
This reminds us that this time is not different. It is the same as all the previous ones. A bubble created from monetary policy gives way to a deep hangover.
The U.S. technology sector, which soared thanks to very low rates and high liquidity, began to show signs of weakness, and the U.S. market reacted by losing support levels as a continuation of the five-year lows in China and emerging markets as well as ongoing weakness in Europe, showing that the United States was not immune to the problem of excesses in other markets and that “value” in Europe or emerging markets is not existent.
These markets fell with the United States—and more in some cases. The U.S. market might be expensive, but others are optically cheap yet very expensive in reality. As such, they fall in tandem.
Problem Starts With Wrong Diagnosis
If we look at the 180 most important economies in the world, only six have an evident improvement of their fiscal and commercial imbalances in their forecasts for the next few years. In other words, almost no government in the world plans to reduce the rate of debt increases, let alone the public debt.
If we look at the corporate sector and households, the situation is much better, because private debt is somehow more contained—except in China—and especially in terms of solvency, compared to profits and assets.
Given that it is more than likely that central banks will continue to Japan-ize the economies through financial repression, these “red cards” are becoming more frequent and, in addition, there comes a point at which the saturation of monetary and debt measures stops working even as a placebo.
Governments and their central banks always start from a wrong diagnosis. They always believe that the problems of their economies are due to lack of demand and that turmoils are caused by external enemies, not by their policies.
By appointing themselves as a solution to the problems they create, they only perpetuate the imbalances, and the solution is increasingly complex.
Above all, the tools that central banks and governments have always used—lowering rates, increasing liquidity and increasing spending—generate very evident diminishing returns. In the past eight years, for every $1 of GDP, there were $3 of debt created.
The incentive to continue inflating the risky assets is high. However, we already have had several warning signs, and we keep ignoring them. Even worse, episodes of volatility are being used to increase imbalances and generate further problems in the long-term.
When societies are based on promoting spending and debt, not saving and making prudent investments, we are always going to throw ourselves into a bigger problem based on the conviction that nothing bad is going to happen.
When it bursts, governments and central banks will blame anyone except themselves. And repeat.
Daniel Lacalle is chief economist at hedge fund Tressis and author of “Escape From the Central Bank Trap,” published by BEP.
Views expressed in this article are the opinions of the author and do not necessarily reflect the views of The Epoch Times.

domain: finance


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Since dietary fiber promotes a feeling of fullness, you can feel satisfied with fewer calories. Have the delivered to your home or office. Things that harm your health, drinking alcohol and taking drugs can harm your health and cancel out the effects of a good diet and exercise. Sure, diet allows you to eat a wide range of delicious food without compromising your.
It should be part of a balanced diet because it's the main part of most meals. Since obesity in children is climbing, schools and parents should consider what their children are eating for lunch and how to make sure that they have adequate nutrition. This nutrition is hard to come by in other types of foods in one's diet. Because what.
It also is lower in sodium than the typical diet, and includes menus with two levels of sodium, and, mg per day. After you write up your meal plan, make time to go grocery shopping to stock up on a variety of your favorite healthy items. Not only is eating colorful food fun, but it is also a good indication that you're eating plenty of good nutrients and antioxidants. Fats form a layer beneath our skin.
Simply explained, having a balanced diet is very crucial for body functioning. The foods we eat affect us more than we realize. Most fast food and restaurant chains also offer nutrition information online. Since your developing baby requires a considerable amount of calcium, your body will take calcium from your bones, if you do not consume enough through your diet should consume at least servings of protein daily. Not only can.

domain: food


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Jasper Vacation Rentals by Expedia are designed to cater to the diverse needs and preferences of travelers. Whether you’re seeking a cozy cabin nestled amidst towering pines, a spacious chalet with stunning mountain views, or a luxurious condo in the heart of town, there is an accommodation option to suit every taste.
Expedia understands the significance of a seamless vacation experience. Therefore, each Jasper Vacation Rental is meticulously inspected to meet the highest standards of quality and cleanliness. From the moment of booking until check-out, guests can rely on the dedicated support team to provide personalized assistance, ensuring a stress-free and enjoyable stay.
Expedia offers the best Jasper vacation rentals
1. Downtown Jasper Suite
The Downtown Jasper Suite, offered by Expedia, is a remarkable choice for those seeking unforgettable vacation homes in Jasper. As you step into the suite, you’ll immediately feel a sense of warmth and elegance. Speaking of adventures, one of the many advantages of staying at the Downtown Jasper Suite is its prime location.
Within walking distance, you’ll find a wide array of restaurants, cafes, boutiques, and art galleries, allowing you to immerse yourself in the vibrant atmosphere of downtown Jasper. Of course, the main allure of Jasper lies in its breathtaking natural landscapes, and the Downtown Jasper Suite offers easy access to explore them.
2. Downtown Jasper Suite Beautiful Views
Located in the heart of downtown Jasper, the Downtown Jasper Suite Beautiful Views is a top choice for travelers seeking a memorable stay in this charming Canadian mountain town. With its proximity to a variety of shops, restaurants, and attractions, guests can easily explore all that this picturesque town has to offer. Step inside the suite, and you’ll be greeted by a beautifully furnished space designed with both style and comfort in mind.
With its central location, comfortable accommodations, and stunning views, the Downtown Jasper Suite Beautiful Views is undoubtedly one of the most sought-after Jasper vacation rentals.
3. Miette Mountain Cabins
Located in the charming town of Jasper, Miette Mountain Cabins provide an idyllic base for exploring the wonders of the Canadian Rockies. Jasper National Park is a haven for outdoor enthusiasts, and Miette Mountain Cabins offer easy access to a multitude of activities. When it comes to Jasper vacation rentals, Miette Mountain Cabins stand out for their exceptional service and commitment to guest satisfaction.
When it comes to Jasper vacation rentals, Miette Mountain Cabins stand out for their exceptional service and commitment to guest satisfaction. The surrounding trails and scenic vistas provide endless opportunities for exploration and adventure.
4. Jasper East Cabins
Nestled in Alberta, Canada, Jasper is a picturesque town renowned for its stunning landscapes, including towering mountains, sparkling lakes, and lush forests. With its pristine surroundings and tranquil ambiance, Jasper promises an unforgettable vacation experience. Jasper East Cabins by Expedia offer an array of thoughtfully designed vacation homes that combine comfort, style, and convenience.
Jasper East Cabins boast a prime location that offers easy access to the area’s most popular attractions. With their prime location, cozy accommodations, and a range of modern amenities, these cabins provide an idyllic retreat in the heart of the Canadian Rockies.
5. Country living in town limits
While living in Jasper, you’ll be enchanted by its small-town charms. The community exudes a warm and welcoming atmosphere, where locals and visitors alike form a tight-knit community. Located within the town limits, this vacation rental allows you to enjoy the best of both worlds. It offers a peaceful retreat surrounded by picturesque landscapes, rolling hills, and lush greenery typically associated with the countryside.
Despite its rustic charm, the vacation rental ensures that you don’t have to compromise on modern conveniences. Explore the nearby quaint towns, visit local markets, indulge in farm-to-table dining experiences, or embark on outdoor adventures such as hiking, biking, or horseback riding.
Standout features of Jasper vacation rentals
Jasper Vacation Rentals by Expedia offers a wide range of exceptional features that make it the perfect choice for your stay in Jasper. Here are some standout features of Jasper Vacation Rentals:
- Extensive Selection: Jasper Vacation Rentals provides an extensive selection of accommodations, ensuring that you can find the perfect rental that suits your needs and preferences. Whether you’re looking for a cozy cabin, a spacious lodge, or a stylish condo, Jasper Vacation Rentals has it all.
- Unparalleled Convenience: With Jasper Vacation Rentals, you’ll experience unparalleled convenience. The properties are strategically located in and around Jasper, placing you in close proximity to the breathtaking natural wonders and attractions that the area has to offer.
- Exceptional Comfort: Comfort is paramount at Jasper Vacation Rentals. Each rental is thoughtfully designed and furnished to provide a home-away-from-home experience. You can expect plush beds, well-equipped kitchens, cozy living areas, and modern amenities to enhance your stay.
- Spectacular Views: Many of the Jasper Vacation Rentals boast spectacular views of the surrounding mountains, lakes, and forests. Immerse yourself in the awe-inspiring beauty of Jasper National Park right from your rental property.
- Personalized Service: The dedicated team at Jasper Vacation Rentals is committed to ensuring your stay is exceptional. They provide personalized service and are readily available to address any inquiries or requests you may have during your visit to Jasper.
- Flexibility and Privacy: Jasper Vacation Rentals offer flexibility and privacy, allowing you to create your own schedule and enjoy your vacation at your own pace. You can relax and unwind in the comfort of your rental without the constraints of a typical hotel experience.
- Value for Money: Choosing Jasper Vacation Rentals offers great value for your money. The rates are competitive, and you get the added benefits of spacious accommodations, fully equipped kitchens, and the ability to share the cost with your travel companions.
- Local Expertise: Jasper Vacation Rentals is backed by Expedia, a renowned travel company with a wealth of local expertise. They can provide recommendations on activities, dining options, and insider tips to ensure you make the most of your time in Jasper.
In conclusion, Jasper Vacation Rentals by Expedia offer an unbeatable opportunity to immerse yourself in the extraordinary beauty of Jasper while enjoying the comforts of a home-away-from-home. With a range of meticulously curated properties, impeccable service, and unrivaled locations, Expedia ensures that your stay in Jasper is nothing short of exceptional. For more information, visit Heybucketlist.

domain: geography


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Design by Spagnola and Associates
Art direction: Tony Spagnola
Design: Nico Cutis + Kyle Green
Cummins approached Spagnola & Associates with the opportunity to design exhibits in the Cummins Technical Center building designed by Harry Weese in 1968. The exhibits include an engine parts wall located at the entry to the customer dining rooms that is composed of over 500 engine parts and a historic patent display located in the Technical Center Laboratories. The patent display celebrates Cummins technical patents from 1916 to present.
Photographer: Brad Feinknopf

domain: design


Mattress toppers are generally used in providing more comfort by burning off and developing a mattress that's too much or firm while encouraging your physique. As they are usually soft the majority of those toppers do work in improving a sagging mattress. For this instance, a brand new mattress is the thing you want instead of a fresh topper. Mattress toppers come in lots of different fabrics, thicknesses and sizes. Locating the ideal mattress pad will be dependent in your own personal sleeping habits and your requirements. Go here: beddingnbeyond for details.
However, mattress pads are preferred by many if you are more suitable and more inexpensive. They may be transportable and wont cost you plenty of money. To acquire the foam mattress topper, you'll find lots of things to consider when selecting one.
Just like bed sheets, beds, beds, and covers, foam mattress toppers also come in different sizes. As different companies might have measurements of bed size, it's immensely important that you measure the width and duration of the mattress for which you want to receive a foam topper. In this way you'll be able to ensure the fit of the topper and the mattress will fit for better sleeping quality.
Pads for mattresses have been sold in various thickness's. One-inch or two-inch foam toppers can offer a feeling while ones can help improve the feel and texture of one's own mattress. A lot of folks opt for 4-inch or even 3-inch toppers for a comfortable sleeping experience. People who have a budget have a tendency to prefer 2-inch toppers or toppers which are somewhat less thick.
Density denotes the burden of one cubic foot of a cushioned mattress. The greater the density, the better your memory foam mattress topper in responding to human body temperature, conforming to weight, and providing human body support. Denser foam is also more durable than the dense types. People who have human anatomy and joint pain are more comfortable with memory foam toppers with a density of 4 lbs or longer. On the flip side, people that have no joint disorders or some other issues would be comfortable with a 3-pound density.
You'll find two types of foam mattress topper; people created from latex and out of polyurethane foam. Latex toppers are made from the pure sap of rubber bands are natural, porous, and biodegradable. Memory foams are watertight products derived from petroleum. Regardless of material, both types offer support and luxury relaxation to your back, shoulders, neck, and limbs. Both latex and polyurethane foam are also hypoallergenic and resistant to mould, mildew germs, and dust. The major difference between these two types is that latex toppers are elastic and lively atmosphere, while memory foams toppers are quite rigid.
Although hypoallergenic, foam mattress toppers attract dust, blot , and dirt easily. Protecting them is recommended. Choose covers produced from 100% cotton for the comfort. The covers can be also valuable in resisting equilibrium in memory foams and slowing the degradation of latex. With suitable zippers, those cotton covers are easily removed and washed to keep up hygiene. Nevertheless, make sure should you not want your pay to 18, to just dry-clean the cover.


While Android has a stronghold over the smartphone market, owing to their features, the iPads were more dominant compared to Android tablets. However, last year this scenario has turned around.
According to market statistics revealed by Gartner, Android tablets, for the first time in 2013, have had more sales globally compared to the Apple iPads. Not just that, the number of Android tablets shipped in 2013, was more than double that of the Apple iPad. As many as 121 million Android tablets were sold in 2013 compared to Apple’s 70.4 million iPads.
Android tablets had a sudden surge last year, with the platform now occupying 61.9 percent of the market share compared to last year’s mere 40 percent. iOS and Windows accounted for the remaining 36 percent and 2.1 percent respectively. It’s quite obvious that the ultra-low-priced Android tablets like Nexus 7 have helped the platform to grow rapidly.
Speaking about the recent change in trends, Roberta Cozza, research director, Gartner, said, “In 2013, tablets became a mainstream phenomenon, with a vast choice of Android-based tablets being within the budget of mainstream consumers while still offering adequate specifications.”


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From Our Editors
Medical symptoms may arise when you least expect them, but Beverly Hills's Karl I Norris MD is always prepared to help you. Finding quality medical treatments, such medical check-ups, is easy at this clinic. This clinic features a strict appointment-only policy, providing scheduled guests with timely and professional services. Don't let your health fall by the wayside, and set up an appointment at Karl I Norris MD today.

domain: medical


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How to beat Amazon – a retailer’s guide
Amazon.com may have old-fashioned retailers sweating, but it still doesn’t have brick-and-mortar beat.
Online shopping may increase every year and no one does it better than Amazon.com Inc., which sells just about everything imaginable. It ranked as the 10th-largest retailer in the U.S. with $34 billion in 2012 sales. It was 8th-largest in the world with $61 billion in sales. More noteworthy is its growth. The 30.4 percent rise in U.S. sales between 2011 and 2012 dwarfed all other retailers.
You can see why merchants would be nervous.
But Dublin, Ohio-based WD Partners Inc. says don’t pack up the store yet. The retail consulting and design firm’s newest study, Amazon Can’t Do That, surveyed more than 1,700 shoppers about that online/in-store divide and found that stores still have several advantages.
“The fundamentals of physical retailing are still strong,” Lee Peterson, executive vice president of creative services, told me.
The answer isn't’t to mimic Amazon (NASDAQ:AMZN), but rather to be better at what stores do best. Peterson said customers overall still like to see, touch and feel potential purchases. Plus, while online shopping has many convenience advantages, it can’t top the instant ownership that comes from old-school, in-store shopping.
Emotion still comes into play so store experience has value, if executed with today’s consumers in mind, Peterson said.
Dan Eaton covers retailing and restaurants for Columbus Business First.
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Overfishing-The Threat to Water Life
Overfishing is the biggest threat to water life. We are losing many important species of fish due to this issue. No doubt, today, fish capturing is a significant way to get protein an income. At the edge of this poverty, it is the livelihood of a lot of people. The coastal communities are totally dependent on fish. It is the need of the hour to understand the issues of these people and stop people from eating the seafood that is at the edge of extinction.
In the past fishing was not that dangerous and was sustainable. It was because they did not know the latest technologies and methods to catch fish. They had the limits of sources and vessels to catch them. Due to this, they were able to catch only a limited number of fish.
What is meant by Overfishing?
Overfishing is a way of fish catching in which people catch fish more than they need. Due to this reason, the population of that specific breed starts to diminish. It becomes very tough to recover the depleted species. With commercial fishing, people catch a lot of many other sea creatures and then discard them. So, overfishing, not only affecting the number of the specific fish, but also the other sea creatures and animals. The prolonged fishing causes severe damage to the world’s assets.
Overfishing is damaging the ecosystem and that is resulting in the disturbance of the food chain. We all know that a major portion of the earth’s population is dependent on fish. As a result of this issue, they are losing their important source of protein. If this situation persists, we will face serious issues of the food crisis. It is expected that the seafood will be banished from the earth by 2048.
How Overfishing is affecting World?
Overfishing is causing serious damage to the world. We all know that global warming and greenhouse gases are already causing so much damage to ocean life. Due to the increasing temperature, the fish’s life is threatened. But, humans are causing more damage to them than climate changes. Bluefin Tuna is the favorite fish of most of us, we all love to have them in Tuna salad. But, do you know that the population of Bluefin Tuna has decreased to 96% in the last century.
Though there is consumption regulation, the population is decreasing. The fish species are facing unsustainable damage and their reproduction rate is also lowering. This is the most serious issue. It is because of the reason that humans catch juvenile and adult fish without discrimination. As a result, the number of fish that can reproduce is lowered. It is the most serious issue that should be noticed in order to save fish species. Poor fishing management is the major cause of fish population depletion.
How we can control Overfishing?
When some issues happen in the world, everyone says we cannot control it alone. But, did you think ever that first step leads you to the destination. So, if you cannot control all the people, just make yourself right. You can do the same in case of Overfishing. Let’s take the first step. You can protect those cute fish by lowering the consumption of seafood. Because you can get protein from a lot of other sources. I understand that sushi is your favorite seafood. But, to save the world’s fish population, you need to skip it. Just try at once, it will make a pretty good difference. If we will ignore this disastrous situation a time will come when there will be no fish left on the earth.
So, it is your duty to tell the world that there must be laws for fishing. It is a need of the hour for all of us and leaders to take serious action against Overfishing. There should be smarter management systems that will be known as fishing rights. The under fishing rights will work more for them. The government should announce the improvement in the income of fishermen with an increase in the fish population. It will work more for the protection of the fish population. No doubt, it is the most sustainable strategy that can save our species.

domain: biology


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Hans von Holst
Karolinska Institute, SwedenReceived Date: 2022-06-10 | Accepted Date: 2022-06-17 | Published Date: 2022-06-30
Cytotoxic brain tissue edema, which is found in both grey and white matter cells, is a complicated secondary consequence to ischemic injury following cerebral diseases such as traumatic brain injury (TBI) and stroke. To some extent the pathophysiological mechanisms are known, however far from complete. A new hypothesis regarding the etiology to cytotoxic brain edema is presented. The hypothesis is that external energy due to TBI and internal energy due to mechanical forces following stroke results in the disruption of non-covalent and covalent bonds in protein and nucleotide structures. The unfolded proteins attract water molecules while the disruption of nucleotides such as adenosine-tri-phosphates causes a dysfunction In ion hemostasis and which may tentatively explain the etiology to cytotoxic edema. Our studies using computer models show that the kinetic energy following an impact to the head has the potential to break the chemical bonds in the protein and nucleotide structures resulting in cytotoxic brain tissue edema. Since folding of mature proteins is very much dependent on normal energy supply, the protein synthesis cannot continue during the ischemic process. Under such conditions very little of the energy rich ATP can be produced and which may result in disturbance between extraand intracellular ion metabolism. By using a folded protein in laboratory investigation, the present hypothesis has the potential to be confirmed and hence develop new drugs for therapeutic use.


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On Tuesday, the White House released a report estimating that delaying action on climate change could cause $150 billion a year in damage to the U.S. economy.
“These costs are not one-time, but are rather incurred year after year because of the permanent damage caused by increased climate change resulting from the delay,” the assessment warned.
That same day, President Obama announced moves to help reduce greenhouse gasses. But some critics charge that the President’s actions have so far failed to be proportionate to the crisis the White House predicts.
As DeSmog reported, on Tuesday, the Environmental Protection Agency’s program on natural gas pipeline leaks came under fire from the EPA‘s own internal watchdog. The EPA inspector general lambasted the agency for setting up rules that rely heavily on voluntary leak repairs by pipeline companies while turning a blind eye to state policies that allow those companies to simply pass the price of leaking gas to consumers instead of making costly repairs.
The resulting leaks, the EPA audit concluded, cost consumers over $192 million and the resulting greenhouse gasses each year were equal to putting an addition 2.7 million cars on the road.
On the heels of that report, the Obama administration announced that it would adjust its methane pollution controls — but the measures they announced fell far short of what some experts argue is necessary to curtail methane’s climate hazards. The Department of Energy’s new measures include adjustments to its voluntary leak control program and add funding for research into ways to better curb leaks.
“While we applaud the commitments made by DOE, labor unions, utility groups, and other stakeholders,” Earthworks Policy Director Lauren Pagel told the Oil and Gas Journal, “voluntary measures and new research initiatives don’t adequately protect communities and the climate.”
In recent years, methane leaks — especially those from the nation’s ongoing shale drilling rush — have caught the attention of researchers because of the gas’s powerful climate-changing effects, which are at their strongest over a decade or two.
Because methane traps an enormous amount of heat relatively soon after it is released into the atmosphere — 86 times as much as the same amount of carbon dioxide, according to the UN‘s panel of climate change experts — the harm that it does is much more immediate than other greenhouse gasses. And leaks from the natural gas industry are a major source of methane emissions in the U.S.
“Reducing the oil and gas industry’s massive methane pollution could help provide the breathing room we need to avoid disastrous climate tipping points,” Shaye Wolf, climate science director at the Center for Biological Diversity, said. “The Obama administration has to start using accurate estimates of methane’s short-term climate effects. But our government also has to take swift action against this dangerously potent greenhouse gas.”
Obama’s stance on methane emissions, including the recent Department of Energy announcements, drew protests from some scientists. In a Tuesday letter to Energy Department officials including secretary Ernest Moniz, 21 prominent climate scientists, many of whom have published high-profile papers on methane leaks, called for stronger oversight of emissions from several industry industries, specifically focusing on the oil and gas industry, the agricultural sector, landfills and coal mining.
“[A]ggressive mitigation of methane emissions is essential if the near-term pace of climate change is to be slowed,” the letter warned. “Such a slowing is essential to increase the likelihood of avoiding climatic tipping points and to moderate the intensification of current climate impacts, including Arctic sea-ice loss (which has also been implicated in intensifying extreme weather anomalies), ice sheet melt, permafrost thawing, and declining seasonal snowpack.”
The scientists specifically focused on outdated figures used by federal agencies, calling on the Obama administration to reconsider the way it assesses methane’s role in climate change.
“EPA’s greenhouse gas inventory converts methane emissions to CO2 equivalents using a seriously outdated value,” the letter said. “Because of this shortcoming, the analysis of emissions and their effects in the Methane Strategy requires re-calculation using the best-available updated [global warming potential] values.”
Still some advocates say that the President’s recent moves might be a sign that minds are beginning to change in Washington D.C.
“These rules can be a first step down the road to limit dangerous methane pollution,” Ms. Pagel told the Oil and Gas Journal “and begin to truly shift our energy systems away from an ‘all-of-the-above’ strategy to one that throws the full weight of our resources behind renewable energy.”
Photo Credit: Fire performing practices plugging leaking methane gas, via Shutterstock.

domain: news


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Hashtags, the widely used convention to find tweets on a particular topic, are the stars of a new TV ad campaign from Twitter. This is the first time the social network placed TV spots and they were first aired at the weekend on Time Warner’s TNT channel, during Nascar’s 2012 Pocono 400 race.
Twitter created a total of seven 16-second spots for the event. They show racecar drivers, technical staff or attendees posting photos on the social network as a means to promote the new hashtag pages Twitter introduced last week.
All the ads point viewers to the Twitter.com/#Nascar page, which redirects to twitter.com/hashtag/nascar. The page aggregates through a combination of algorithms and curation relevant tweets and photos posted using the hashtag, giving importance to those coming from the race drivers and attendees.
Although many TV shows now use hashtags to generate conversation, the hashtag page is different from simply searching for a term using Twitter search because you get relevant tweets, not only the latest postings. Also, if you click on the #NASCAR hashtag anywhere on the Web version of Twitter, you will be taken to the special page.
So far the Nascar hashtag page seems to be a one-off — Twitter does not appear to have set up a hashtag page for other events, such as Apple’s WWDC developer conference today, for example. But its use is perhaps an indication of how Twitter is looking at expanding offers for advertisers, who can now buy only promoted tweets.


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WATERBURY -- The letters, written in pencil in the uncertain half-cursive of a 25-year-old soldier, sat on a bookshelf in a New Britain home for 59 years.
After Nicholas DeSimone Jr. was declared missing following a July 13, 1953, battle in the Korean War, someone tucked the two dozen letters he wrote to his family in a safe spot. Later, the letters would be joined by posthumously awarded medals and updates from the military on recovery efforts for the remains of those presumed killed in action.


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Fox & Friends: Americans Deserve To Go To Bed Without Worrying ‘About Being Killed By An Illegal Immigrant’
On the second day of the new year, Fox & Friends picked up right where it left off in 2018 — fearmongering about scary murderous Latino immigrants.
As we entered the 11th day of a partial government shutdown due to President Donald Trump’s demand that Congress include border wall funding in a spending bill, the curvy couch sitters pointed out that while it may be inconvenient for certain services and locations to be closed it was all because Trump wants Americans to got to be without worrying about illegal immigrants murdering them.
After co-host Brian Kilmeade noted that some asylum-seeking migrants have “bad intentions,” he went on to discuss how the inconvenience of the shutdown may “ramp up the pain and if that will improve the process for negotiation.”
Fellow host Ainsley Earhardt then took the baton and ran with it, agreeing that “it is an inconvenience” before parroting Trump’s extremist (and patently false) rhetoric on immigration.
“But the president is saying most of the people are good people, but there are some bad apples in the group,” she said. “And even though it is an inconvenience, he’s saying that your safety, and your security as an American — he said that you deserve to be able to go to sleep at night and not have to worry about being killed by an illegal immigrant.”
Earhardt continued, “And we’ve seen that happen. We’ve seen — there’s so many moms and dads that we’ve interviewed that say ‘yes, it’s very rare that this is gonna happen. But it can happen and it happened to my child.’ And the president is saying ‘I want to prevent other families from going through that loss.’”
This feels like the kind of thing Trump will either tweet out or repeat verbatim the next time he speaks to the press, keeping the Trump-Fox Feedback Loop intact.
Watch the clip above, via Fox News.


Alex Chiasson's goal late in the third period was a difference-maker for Ottawa as they outlasted the Blues to earn a 3-2 shootout victory Tuesday.
Alex Chiasson tallied a goal in Ottawa's 3-2 victory over Nashville on Thursday.
Alex Chiasson returned to action on Tuesday November 11.
Alex Chiasson (foot) is projected to be a game-time decision on Tuesday.
Alex Chiasson will not play in Sunday's game against Toronto with an undisclosed injury.
Alex Chiasson is expected to return from a foot injury on Thursday.
Alex Chiasson sat out Tuesday's game versus Detroit with a foot injury.
Alex Chiasson has a five-game point streak.
Alex Chiasson got his first goal in an Ottawa uniform during Thursday's season opener at Nashville.
After coming over in a trade with the Dallas Stars, Senators forward Alex Chiasson is looking forward to a fresh start in Ottawa.
Alex Chiasson started training camp skating on the Senators' second line alongside Mika Zibanejad and Milan Michalek.
Alex Chiasson is looking forward to playing in Ottawa.
The Dallas Stars have sent Alex Chiasson, Nicholas Paul, Alex Guptill, and a 2015 second round pick to the Ottawa Senators in exchange for Jason Spezza and Ludvig Karlsson.
Alex Chiasson scored a goal in Dallas' 3-2 loss to Anaheim in Game 2 on Friday evening.


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Ethereum (ETH) creates much debate in the crpytocurrency world about whether or not the overtaking of Bitcoin is possible. Since its inception in 2014, ETH radiates an aurora of trust and hope about being the golden standard for cryptocurrency. This reputation results from not only as a result of the technology that supports it, but also from its fearless leader Vitalik Buterin. Looking at its short history, it is no secret that the pace of growth and adoption has been rapid. The question now is whether ETH can maintain this growth while still pushing the frontier for security. The answer remains unknowable for now, but what many agree on as being true is that Buterin and ETH have the best chance of leading the cryptocurrency revolution.
The info graphic below recounts the journey ETH has had in recent years. When ETH’s achievements are put side by side with each other, there is no doubt about its already existing impact.
“The history of Ethereum” graphic was given to ReadWrite for publication by the team at www.ethereum-kaufen.de.


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Series: Bride Train #1
Author: Reece Butler
Publication Date: August 2010 by Siren-Bookstrand
Genre: historical romance/menage
Back Cover Blurb:
Sheriff Chambers banned the Elliotts from town until one got a wife and settled them all down. Finding a defiant Trace Elliott in town, the sheriff offers a tall, ornery barefoot woman to solve all their problems.
Beth is shocked how the stranger’s touch inflames her and mortified the next morning when hotel patrons comment on her amorous wedding night cries. She discovers the Elliott men share everything and intend to seduce her into agreeing. Trace, Simon and Jack heat her blood, but do they care for her, or only what she provides? Then Big Joe offers gold to bring her to him…
I loved getting to know the characters that Reece has developed for this chemically charged tale. Trace’s strength of character yet unassuming attitude towards himself was both a contradiction and an endlessly endearing character. His brothers’ loyalty towards him added to this unmistakable, indescribable aura that surrounds him. Beth was the perfect woman to throw into this mix. Her strength of character is tempered by the misconception of herself that was perpetuated by her family. I loved seeing these four make a family of their own while also lighting the pages on fire.
This was a delightfully quick, sinfully sizzling read. It was my intro to Butler’s work, but I’m definitely hooked now! I can’t wait to delve further into her repertoire.

domain: library


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Road to USP <800> Compliance
Section 15: Deactivating, Decontaminating, Cleaning, and Disinfecting
Sections 1 through 14 of USP Chapter 800: Hazardous Drugs—Handling in Healthcare Settingsprovides the blueprint for safely getting a hazardous drug into our facilities and compounding. On our road to compliance, Section 15 provides us with a very comprehensive overview of the concept of ‘cleaning’ and its importance in the process of safely handling hazardous drugs.
IMPORTANT: Isopropyl Alcohol is NOT a cleaning agent.
Sterile compounding requires a robust contamination control program that must consider personnel and material flow; personnel gowning, training and behavior; aseptic manipulation, interventions management, and environmental monitoring. Integrated within this complex system lies cleaning and disinfection. The concept of a formal cleaning program was brought to light with the introduction of USP <797> in 2004. Prior to the introduction of this minimal practice standards document, compounding locations classified cleaning as a non-formal process in the management of medications. Hospital pharmacy departments, due to the nature of state regulations, accreditation interpretations and fear of pilfering, often limit environmental services (EVS) from conducting formal cleaning programs for which they have been trained. This limitation of EVS to pharmacy departments has relegated the cleaning processes to pharmacy staff with varying, inconsistent and inadequate results due to lack of training and validation.
The Food and Drug Administration (FDA) has highlighted the concern over the cleanliness of compounding conditions for medications for patients in their recently revised guidance document ‘Insanitary Conditions at Compounding Facilities Guidance for Industry.’ In the introduction the FDA reminds us that, “Under section 501(1)(2)(A) of the Federal Food, Drug, and Cosmetic Act 351(a)(2)(A)), a drug deemed to be adulterated ‘if it has been prepared, packed, or held under insanitary conditions whereby it may have been contaminated with filth, or whereby it may have been rendered injurious to health’.” Although not an enforceable document, it serves as a guidance for the protection of the public. The guidance document clearly states, ‘Drugs (including biological products) prepared, packed, or held under insanitary conditions are deemed to be adulterated, regardless of whether the drugs qualify for exemptions set forth in sections 503A or 503B of the 28 FD&C Act,’which encompasses hospital and alternate care locations. The unfortunate impetus for FDA publishing this guidance is based on ‘insanitary conditions that FDA has observed’on inspections of compounding locations which include hospitals, 503A pharmacies, 503B compounding manufacturers and the pharmaceutical industry. FDA states the scope of the guidance ‘are applicable to both sterile and non-sterile drug production.’
Proposed revisions to USP <795> Pharmaceutical Compounding – Non-Sterile Preparations, USP <797> Pharmaceutical Compounding – Sterile Preparations, and, proposed USP <800> Handling Hazardous Drugs in Healthcare Settings each have sections devoted to cleaning and surface sampling. Proposed/revised USP <795> defines Cleaning as “The process of removing soil (e.g., organic and inorganic material) from objects and surfaces, normally accomplished by manually or mechanically using water with detergents or enzymatic products.”,, Proposed/revised USP <797> defines a Cleaning Agent as; “An agent for the removal of residues (e.g., dirt, debris, microbes, and residual drugs or chemicals) from surfaces,” and, proposed USP <800> adds complexity to the process by building on the ‘cleaning’ definition under section 14.4 Cleaning C-PEC and Other Devices Used for Compounding HDs by adding the additional steps of Deactivation, Decontamination, Cleaning, and Disinfecting.
Historically, sites compounding medications for patients have customarily used 70% isopropyl alcohol as a ‘cleaning’ agent. However, isopropyl alcohol is not a cleaning agent; it is a disinfectant and does not meet the definitions listed within the noted USP standards as a cleaning agent. The use of isopropyl alcohol as a misunderstood surrogate cleaning agent in non-cGMP compounding locations has been employed without a validation process to support the effectiveness of the agent. As noted, for an agent to be defined as a cleaning agent it must remove dirt, debris, microbes and drug residues. The lack of cleaning-ability of isopropyl alcohol is most evident with hazardous drug compounding.
For more than 30 years, studies have found residues of hazardous drugs present in measurable concentrations throughout the environments where they are handled. We also know that these residues can carry-over throughout the line of handling—from the receipt of the drug at the loading dock to compounding, to administration, and to its final disposal.
The goals for the USP <800> cleaning program must be viewed as protective for the patient, protective for all healthcare individuals all the continuum of handling and the environment. For sites to be compliant with USP <800> for cleaning, they must be compliant with the requirements set under USP <795> for non-sterile and USP <797> for sterile pharmaceutical preparations. Establishing a cleaning program for hazardous drugs must have both under-chapters as the base to build from and sites should not establish a program in a vacuum. USP <800> has devoted an entire section to cleaning, highlighting the importance. Section 15 outlines the 4-step process of DEACTIVATING, DECONTAMINATING, CLEANING, AND DISINFECTING noting that not one single method or cleaning process exists as a universal standard for all hazardous drugs. Due to the importance of the 4-step process, USP <800> defines each step and provides the ‘why’ for each step with the goal of removing hazardous drug residue, returning the cleaned location to baseline (no-residue or contamination), not damaging the cleaned, and providing a suitable work environment to protect personnel and patients. Simplistically defining each step will help staff understand the importance of each step:
Deactivation is intended to render any hazardous drug surface contamination inert or inactive. It is important to recognize that in terms of deactivation, there is no one proven method for inactivating all compounds. EPA-registered oxidizing agents represent the most widely used option and should be used when possible (e.g., peroxide formulations, sodium hypochlorite, etc.). However, it is important to recognize that agents are caustic, and products such as sodium hypochlorite will pit or stain stainless steel surfaces if left in contact too long.
Decontamination focuses on inactivating, neutralizing and physically removing surface contamination by the deactivation agent and hazardous drug residue and transferring it to sterile, lint-free, absorbent, disposable materials. Chemicals such as sodium thiosulfate can help neutralize chemicals used in the deactivation step to minimize corrosion and pitting of stainless steel. As a bonus to enhancing the cleaning process, this step should be strongly considered for each drug vial that may come contaminated from the manufacturer. Applying this step to vials can reduce contamination introduced into the sterile compounding engineering controls (hoods). It is important to ensure that the solvent used for wiping vials does not alter the product label.
Cleaning is intended to remove contaminants from surfaces using water, detergents, surfactants, solvents or other chemicals, and the Cleaning section in Chapter <797> is appropriate for both hazardous and nonhazardous drugs. It is very important to make sure that any products used for cleaning do not introduce microbial contamination. Facilities should look to the product material specifications to ensure they are EPA-registered to meet the five “-cidal” criteria: bactericidal, fungicidal, virucidal, tuberculocidal and sporicidal. If an agent states that it “kills spores” or that it kills a specific type of spore, that is not the equivalent of being labeled as a sporicidal agent. If a product that is being used is not clearly labeled as sporicidal, a sporicidal-labeled agent should be added to a scheduled cleaning regimen. Another important note about cleaning agents is the contact time of an agent with a surface to induce the specific -cidal response. Some agents require up to five minutes of direct contact time to be effective, meaning applying the agent in the defined quantity and allowing it to stay on the surface for the noted time. Wiping away the agent(s) too soon removes the benefits of the cleaning agents and may allow microbes to proliferate.
Disinfection is intended to inhibit or destroy any microorganisms and must be done for areas needed to be sterile. EPA-registered disinfectants and/or sterile 70% isopropyl alcohol are appropriate agents for this step. The use of ultraviolet light as a means for disinfection should only be considered as an adjuvant to physically applying and removing liquid disinfecting solutions. The biofilm that might be left on surfaces can be removed with the physical wiping motion.
Following the cleaning process, it is important to examine the areas for visible residue that may be left behind by some products, often denoted by hazy/white-ghost smears or drops. Visible residue is unacceptable, and it must be understood that dried chemicals no longer possess their desired activity. Dried residue is considered a contaminant and represents potential air pockets between the surface and the residue that can harbor spores and can easily be transferred to the sterile field or products. In addition, dried residue left on surfaces can lead to corrosion of the surfaces if not removed for long periods. Regulatory inspectors often see residue as an indication of inadequate cleaning and the FDA issued a guidance document on the concern of residues.
As sites define each location where hazardous drugs are handled, they must employ certain steps of the 4-step cleaning program. For example,non-sterile areas where HDs are handled (receiving containment ventilated enclosures (CVE)) and reusable equipment and devices (counting trays; spatulas; unit dose devices) must be deactivated, decontaminated, and cleaned. For sterile preparation areas, as directed by USP <797> must include the final step of disinfecting. It is important that cleaning solutions that are selected are not reactive to surfaces to be cleaned and will not harm equipment or impact the protective nature of devices employed to provide safety (e.g. melting surfaces, pitting stainless steel, melting casing of electrical wires, penetrating gloves, impacting the HEPA filter seals in primary engineering controls).
Clearly written standard operating procedures must be in place and should include the specific name of defined chemicals used for the 4-step cleaning process, any dilutions of solutions, assigned expiration dates to on-site prepared solutions, frequency, and documentation steps.
The process of employing the cleaning methods listed should be classified as a hazardous process, thus, requiring formal education and documentation of training of personnel performing these activities. Sites must clearly define what personal protective equipment must be donned when handling cleaning solutions. Noted cleaning solutions can be caustic to skin and may illicit respiratory reactions. All personal protective equipment (PPE) must be vetted to demonstrate they are resistant to the cleaning solutions use. It should not be assumed that hazardous drug rated PPE is suitable for all cleaning solutions. As a starting point sites should review the literature of their PPE and consider the use of two pairs of hazardous drug gloves rated to ASTM 6978D and impermeable disposable gowns rated to ATM 739. Since the process of cleaning has the potential to splash sites should strongly consider the use of tight-fitting eye protection or face shields. As noted, some solutions may require the addition of respiratory protection beyond a ‘paper-mask’ and sites should consider a fitted N95 mask and to assist solutions with nauseous odors, a carbon based R95 mask.
The World Health Organization (WHO), released a report identifying hospital cleaning solutions as a potential cause of respiratory and reproductive disorders, eye and skin irritation, central nervous system impairment, cancers and other human health effects. Under the U.S. Occupational Safety and Health Administration’s (OSHA) Hazard Communication Standard (HCS) (29 CFR 1910.1200(g)), chemical manufacturers, distributors or importers must provide SDS (formerly known as material safety data sheets or MSDS) to communicate the hazards of hazardous chemical products. The SDS includes the properties of each chemical; the physical, health, and environmental health hazards; protective measures; and safety precautions for handling, storing and transporting the chemical. Sites should share with all staff, especially those with active airway diseases (asthma, COPD), the Safety Data Sheets for cleaning solutions and an employee assessment of risk to exposure must be conducted.
The application of cleaning solutions should be with equipment designed for cleaning cleanrooms and not ‘over-the-counter’ equipment that may react or melt due to repeated exposure. Cleaning equipment should themselves be placed on a routine cleaning schedule and sites should define when equipment must be replaced due to wear/ tear and contamination-risk. Cleaning solutions should be poured onto disposable, low-linting wipes and not ‘sprayed’ due to the aerosolization of the solution(s) and the potential to aerosolized moistened hazardous drug residue. All cleaning materials and PPE must be considered contaminated and disposed according to state and facility policies for hazardous materials.
USP <800> Requires More Frequent Cleaning Than Traditionally Practiced
Twelve published papers have strikingly demonstrated measurable residues of drugs on the outside of vials, accompanying package inserts and outer shipping boxes of vials. USP <800> highlights sites can reduce the amount of contamination by wiping down all vials prior to placing them on any surfaces (preparation tables, staging bins, primary engineering controls). It important that the cleaning solutions used for this process not impact the readability of the label.
In addition to wiping down each hazardous vial, sites must clean their containment primary engineering controls at least daily and the compounding surface of the containment primary engineering controls must be decontaminated between each unique drug to prevent any potential cross contamination of products. This process is clearly supported by the previously mentioned 2018 FDA Guidance Document on Insanitary conditions. As an example, case reports have demonstrated cross contamination of BCG to sterile compounded products subsequently prepared, leading to patient harm and deaths. The deactivation, decontamination, cleaning should immediately take place in the presence of spill, with the addition of disinfecting the surface for compounding surfaces. To minimize the exposure of hazards to maintenance and certifying personnel, surfaces should be cleaned prior any servicing by personnel outside of the department.
Containment primary engineering controls are designed to circulate ISO 5 classified air in a ‘unidirectional’ pattern. To accomplish this process, their design may include areas under the compounding work surface trays, (Figure from Baker). These under-spaces assist with moving air through vents located near to the compounding surface to move contaminates away from the compounding surface. Due to this design, these under-spaces can accumulate hazardous drug residues/spills and other items used during the compounding process (vial caps, syringe packaging, pens, alcohol swabs). USP <800> clearly states that the under spaces must be cleaned (4-step process) on a monthly basis to reduce contamination build-up. It should be noted that access to the under space may be difficult and may require assistance with lifting and holding the upper work surface in place during cleaning. The process of cleaning this surface will disrupt the protect airflow of the containment-primary engineering control and should be classified as a hazardous process requiring additional PPE and specialized training. Sites are encouraged to check with the manufacturer’s maintenance information on the proper process for accessing the under spaces of containment-primary engineering controls.
Commercially Available Cleaning Systems
Currently, the U.S. market has a variety of integrated cleaning systems. These systems have made a point to ease the complicated cleaning process for hazardous drugs. Some systems employ the use of pre-saturated wipes of cleaning solutions used for each step of the cleaning process. It is important to note that some systems may not address each of the 4-steps, thus requiring sites to supplement the step with an additional product. Examples of cleaning systems: Surface Safe®; HDClean®; VIA Wipe 1-2-3®; Peridox RTU®; Pharma-Surface-Guard®.
Some vendors have enhanced their testing to validate that their products can be used for multiple steps of the 4-step cleaning process.
For any product(s) that sites may choose to use, you must get validation from the company that demonstrates the desired result of the product(s). In addition, sites should work with their infection control, employee health. Safety and EVS departments to assist with the selection, training and monitoring the use of products.
Assessing Cleaning Programs
Due to the increased number of hazardous drug wipe sampling test kits, sites can use results as a process to validation cleaning practices and cleaning solutions. There are the traditional wipe analysis kits which quantify defined hazardous drugs and the newly introduced quick test systems that detect the presence of defined residues without quantifying. Proposed USP <800> recommends conducting surface sampling for hazardous drug (HD) residue ‘routinely.’ The chapter recommends an initial wipe analysis to establish a baseline and every 6 months thereafter or as determined by the needs of the site. When a facility begins the process of redesigning and reconfiguring workspaces to meet USP <800> standards, the ideal time to conduct a wipe analysis is prior to any drugs being brought into the space, as this provides a true baseline. To assist sites with conducting consistent wipe analysis, commercially available wipe kits are available. It is important to note, these commercial kits only test for a handful of specific hazardous drugs and the results do not represent all drugs. As such, non-detectable results from a specific analysis do not guarantee that no HD residue is present. Result assessment is further complicated by the fact that there are currently no standards for acceptable limits for residues; however, the goal should be a zero tolerance of measurable residue(s).
Sites have not fully embraced the process of conducting hazardous drug wipe analysis. This was illustrated in the 2017 CriticalPoint survey of annual compliance with 454 hospitals reporting and only 13% (N= 59/454) of sites reported ever conducting an environmental wipe sampling for hazardous residue.
Best practice for a hazardous drug safety program would be to wipe analysis to go beyond defining a historical issue and concurrently validate processes within the hazardous drug continuum. For example, each compounding location (sterile and non-sterile) could conduct an immediate wipe test to confirm surfaces are clean and ready for use. This approach would provide information necessary to help minimize the transfer of residue from surface to surface, or from surface to products destined for patient administration. A recent Danish study demonstrated the use of frequent wipe sampling to assess contaminated locations and improve the cleaning processes to greatly reduce positive samples.
Becton Dickenson (BD) released in 2018 the HD Check Analyzer as a system to provide results in as little as 10 minutes for the hazardous drug residues.
Visante consultants are using HD Check Analyzer in the field. The system requires minimal training for results. The HD Check Analyzer is designed to be an intuitive and easy process, with just 8 steps:
- Assemble supplies and don personal protective equipment;
- Identify test surface using the HD Check template;
- Swab test surface;
- Transfer swab to the sampling tube and invert 5 times;
- Squeeze 4 drops from sampling tube onto the methotrexate or doxorubicin drug assay cartridge;
- Allow 5 minutes for drug assay cartridge to develop;
- Turn on the analyzer and place the developed cartridge in system when prompted;
- Read the positive or negative result
At the time of writing, the system was limited to methotrexate and doxorubicin, which is used at most facilities in the U.S. Unlike the commercially available wipe analysis kits, the HD Check Analyzer checks for the presence of the drug without quantifying the results. The mere presence of residue results in the same response to a quantified sample; recleaning and reassessment to baseline. BD is currently developing a catalog of the most frequently handled hazardous drugs in the U.S.
Sites should consider the continuum of the hazardous drug handling process and assign routing sampling intervals for assessing for residue.
Due to the immediacy of the results, the HD Check Analyzer can be used: daily to validate cleaning processes, whenever cabinets and surfaces where hazardous drugs are used are cleaned, and whenever a spill occurs to validate the spill has been fully cleaned. Conducting real-time wipe analysis to identify any hazardous drug residue serves as a tool that can assist sites with validating their entire hazardous drug handling practices.
Using FDA Guidance Can Enhance Cleaning Validation Check-Points
Sites should use this document as a routine inspection template based on the examples. Selective examples cited for consideration for sites:
“Vermin (e.g., insects, rodents) or other animals (e.g., dogs) in the production area or adjacent areas:” Look at light lens with bugs in areas where drugs are located
– “non-microbial contamination in the production area (e.g., rust, glass shavings, hairs, paint chips).” Look for rust, hair, chipped paint on equipment/walls and exposed drywall
-“Exposing sterile drugs and materials to lower than ISO 5 quality air for any length of time. This would include, … open packages of sterile wipes.” Look at how staff use sterile wipes and where they are located.
– “Producing drugs while construction is underway in an adjacent area without adequate controls to prevent contamination of the production area and product.”
-“Standing water or evidence of water leakage in the production area or adjacent areas” Look for water stained ceiling tiles, dried stains on flooring
-“Handling hazardous, sensitizing, or highly potent drugs (e.g., hormones) with inadequate controls to prevent cross-contamination, including: … inadequate cleaning of rooms, work surfaces, and equipment (e.g., utensils)….” Look at hazardous drug wipe residue test results for positive samples and assess risk of cross-contamination.
-“Using non-sterile disinfecting agents and cleaning pads/wipes in ISO-classified areas” NOTE not required under USP <797>, however, this is a best practice in light of the potential for pathogens to grow in non-sterile solutions (fungal spores, etc.)
– “Lack of, improper, or infrequent use of a sporicidal agent in the facility’s ISO 5 areas and other classified areas.” Look at sporicidal agent in use and ensure labeled as ‘Sporicidal’ and not ‘Kills Spores’ or ‘Kills C. difficile Spores’.
-“Failing to appropriately and regularly clean and disinfect (or sterilize) equipment 306 located in the ISO 5 area.” Look at the process how equipment is cleaned within the PEC (hoods) like IV Workflow hardware; Repeater pumps; collaborative robots
Without conducting a hazardous drug residue wipe analysis, facilities are blindly assuming they their cleaning programs are adequate and they are immune to this widely established pattern of environmental contamination. Conducting regular wipe studies identifies the site’s active risk, allowing the facility to either improve practices or praise staff for following well-defined SOPs. Thereafter, a well-defined, systematic program for routine sampling will assist in monitoring the staff’s diligence at following standard operating procedures.
United States Department of Health and Human Services; Food and Drug Administration Center for Drug Evaluation and Research ; Office of Compliance; Compounding and Related Documents Revision 1: Insanitary Conditions at Compounding Facilities Guidance for Industry; September 2018 https://www.fda.gov/downloads/Drugs Accessed November 19, 2018.
Proposed revision, USP General Chapter: USP <795> Pharmaceutical Compounding – Non-sterile Preparations. http://www.usp.org/compounding/general-chapter-795 Accessed November 19, 2018.
Proposed revision, USP General Chapter: USP <797> Pharmaceutical Compounding – Sterile Preparations. https://www.usp.org/compounding/general-chapter-797 Accessed November 19, 2018.
Proposed, USP General Chapter: USP <800> Hazardous Drugs—Handling in Healthcare Settings http://www.usp.org/compounding/general-chapter-hazardous-drugs-handling-healthcare Accessed November 19, 2018.
United States Health and Human Services: Centers for Disease Control. Guideline for Disinfection and Sterilization in Healthcare Facilities (2008) https://www.cdc.gov/infectioncontrol/guidelines/disinfection/disinfection-methods/chemical.html Accessed November 19, 2018.
Sessink PJM, Anzion RB, Van den Broek PHH and Bos RP. Detection of contamination with antineoplastic agents in a hospital pharmacy department. Pharm Weekbl (Sci). 1992; 14:16-22.
United States Department of Health and Human Services; Food and Drug Administration Center for Drug Evaluation and Research ; Office of Compliance; Compounding and Related Documents. GUIDE TO INSPECTIONS VALIDATION OF CLEANING PROCESSES https://www.fda.gov/ICECI/Inspections/InspectionGuides/ucm074922.htm Accessed November 19, 2018.
Merck BCG Package Insert: https://www.merck.com/product/usa/pi_circulars/t/tice_bcg/ticebcg_pi.pdf Accessed November 19, 2018.
Douglass K, Kastango E. USP <800> Let’s Get Started. Pharmacy Purchasing and Products; December 2017 supplement
Crul M, Simons-Sanders K. Carry-over of antineoplastic drug contamination in Dutch hospital pharmacies. J Oncl Pharm Pract. 2018;24(7):483-489.

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Hop on over to Christine’s blog to see how to make these adorable little creatures. Thanks Emmy & Christine for the great idea! I can’t wait to make them for my kiddos for Easter.
Have you fallen in love with the Art Philosophy Cricut Collection like I have? Would you like to know how to get it for FREE? Be sure to check out this post for more information.
ETA: I just found out that this project idea originally came from Tracey Sanders. Apparently it is so cute that everyone wants to make one and the original designer’s name got lost in the process. I am so sorry about that. Thank you Tracey for designing such an adorable project! You are one talented lady! *Ü*