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Int J Med Sci 2011; 8(5):380-386. doi:10.7150/ijms.8.380 This issue
Prevention of Pleural Adhesions Using a Membrane Containing Polyethylene Glycol in Rats
Volkan Karacam1 , Ahmet Onen2, Aydin Sanli2, Duygu Gurel3, Aydanur Kargi3, Sami Karapolat4, Nezih Ozdemir2
1. Department of Thoracic Surgery, State Hospital, Bilecik, Turkey
2. Department of Thoracic Surgery, Dokuz Eylul University, Izmir, Turkey
3. Department of Pathology, Dokuz Eylul University, Izmir, Turkey
4. Department of Thoracic Surgery, Duzce University, Duzce, Turkey
✉ Corresponding author: Volkan Karacam MD., Department of Thoracic Surgery, State Hospital, Bilecik, Turkey. Phone: +90 (228) 212 10 36; Fax: +90 (228) 212 57 98; E-mail: volkan_karacamcom
Karacam V, Onen A, Sanli A, Gurel D, Kargi A, Karapolat S, Ozdemir N. Prevention of Pleural Adhesions Using a Membrane Containing Polyethylene Glycol in Rats. Int J Med Sci 2011; 8(5):380-386. doi:10.7150/ijms.8.380. Available from https://www.medsci.org/v08p0380.htm
Background: Recurrent thoracotomies regardless of the cause are not a rare occurrence. However, each thoracotomy results in adhesion to some extent. This adhesions increase morbidity and mortality presents a significant inconvenience for surgeons and prolongs the length of operations.
Objective: We investigated the efficacy of Prevadh®, an anti-adhesion agent to prevent intrapleural adesions following thoracotomy in a rat model.
Methods: Twenty male adult Wistar Albino rats were divided into a sham group (Group A, n = 4), a control group (Group B, n = 8), and a study group (Group C, n = 8). Only left thoracotomy was performed in Group A. Group B underwent left thoracotomy, induction of adhesion, and 1 ml saline solution was administered to the thoracic cavity. However, in Group C underwent left thoracotomy, induction of adhesion, and Prevadh® was placed between the pleura and the lung. The rats were sacrificed on day 21, and adhesions were analyzed using both macroscopic and histopathological methods. The results were statistically analyzed. A value of P<0.05 was considered statistically significant.
Results: Mean lengths of adhesion differed statistically significantly among all three groups, while mean intensity of adhesion differed between Group A and Group B, and between Group B and Group C (P>0.05). There was also a statistically significant difference between Group A and Group C in mesothelium proliferation score (P>0.05). No statistically significant differences were found among the groups in terms of pleural thickness, macrophage and mononuclear cell infiltration (P>0.05).
Conclusions: Prevadh® was shown in a rat model to effectively prevent post-thoracotomy adhesions.
Keywords: Thoracic Surgery, Thoracotomy, Tissue Adhesions, Polyethylene Glycols
There are only a few studies on intrapleural adhesions following thoracotomy [1], whereas many clinical and empirical studies have been conducted to investigate adhesions that occur after abdominal surgeries [2, 3]. This is because adhesions following abdominal surgery leads to serious complications, while it is even a desired effect in thoracic surgery, since adhesions that develop between visceral and parietal pleura's after thoracotomy provides a natural pleurodesis effect by preventing postoperative air leakages and pleural effusion. However, these adhesions may cause significant problems in recurrent thoracotomies.
Today, recurrent thoracotomies are being seen with increasing frequency particularly in metastatic lung cancer, unilateral metachronous lung cancer, and recurrent pneumothorax. More than tree resections in a single patient are not a rare condition [4, 5]. Significant adhesions occur in these patients, especially behind the thoracotomy incision line. These scar tissues put surgeons in a difficult position, make it difficult to free the lung and to access to hilus, and causes bleeding and prolonged air leaks [6, 7]. This results increased operation times, morbidity and mortality.
Anti-adhesion barriers are rarely used in thoracic surgeries, and only a few experimental studies have been performed on this subject. Tanaka et al. have shown that adhesions may be avoided following thoracotomy by using a hyaluronate-based absorbable membran in rats [6]. Also, Getman et al. achieved the same effect by using haemostatic membrane [7].
The present study investigates the efficacy of Prevadh® (Tyco/Sofradim, Trevoux, French), which is an anti-adhesion barrier composed of collagen, polyethylene glycol and glycerol following thoracotomy in a rat model. The purpose of this experimental study is to determine the safety and efficacy of this substance before it is studied in clinical trials in humans.
A prospective, randomized, double-blinded, controlled, experimental study was conducted with 20 male adult Wistar albino rats from the same colony weighting 250-300 g. The rats were obtained from the Experimental Animals Laboratory of Dokuz Eylul University Faculty of Medicine. The purpose of using rats is easy availability, safety, and the high ratio of repeating the experiment.
The rats were randomly divided into three groups: Group A: Sham (n = 4) and Group B: Control (n = 8), Group C: Study (n = 8). They were maintained under specific pathogen-free conditions to avoid infections and housed separately in a light-controlled room with a 12:12 h light-dark cycle. The temperature (22±0.5ºC) and relative humidity (65-70%) were kept constant. Standard laboratory rodent chow and water were available ad libitum. They were deprived of food for 12 h before the experiment but had free access to water.
All of the rats were anesthetized by administering ketamine hydrochloride (Ketalar, Pfizer, Turkey) 40 mg/kg and xylazine hydrochloride (Rompun, Bayer, Turkey) 4 mg/kg intraperitoneally. During the procedure, additional doses were administered if necessary. The rats were intubated with 16G plastic catheters. During intubation, the rats were administered 0.1 mg/kg intravenous vecuronium bromide as neuromuscular blocker and, throughout the operation, they received ventilation support in volume-control mode, which provided 90 respiration counts and a volume of 15-20 ml/kg per minute (Hugo Sacs, Rodent Ventilator, Germany). The body temperature was maintained at 37.0ºC with a heat pad to prevent the effects of hypothermia and to maintain the stability of hemodynamic parameters. They were placed in right decubitus position, the operation site was disinfected, shaved, and particular attention was paid for asepsis and antisepsis during operation. Left posterolateral thoracotomy from the 4th intercostal space was performed in all groups.
Only thoracotomy was performed in Group A. Group B underwent thoracotomy, induction of adhesion, and 1 ml normal saline solution was administered to the thoracic cavity (Figure 1A). However, Group C underwent thoracotomy, induction of adhesion, and Prevadh® sized 3 x 3 cm. was placed between the pleura and the lung (Figure 1B). All three groups were checked against bleeding, air leakage, and the layers were closed appropriately. The rats were extubated after they resumed spontaneous breathing, and were kept in separate cages. No antibiotics were administered during or after surgery. The rats received intramuscular morphine HCL 0.1 mg/kg in every 12 hours during the first 24 hours. The rats were sacrificed using ether at lethal doses on day 21, when wound healing was complete and anti-adhesion barrier was completely absorbed.
Induction of intrapleural adhesion model
Adhesion model was generated based on the model in the study by Tanaka et al., which was modified in this study [6]. The parietal pleura was scratched using spanch after the procedure described above. Later, visceral pleura was abraded with dry spanch first, followed by spanch wetted with 0.1 ml iodine, avoiding air leakage and bleeding.
Recurrent thoracotomy was performed at the 8th or 9th intercostal space and intrapleural adhesions were analyzed macroscopically (Figure 1C and 1D). Adhesions were scored as shown below: A) Length of adhesion: The length of adhesion before the first thoracotomy incision (mm). B) Scoring of the intensity of adhesion between the parietal pleura and the lung: 1: No adhesion, 2: Loose: Which can be removed with blunt dissection, 3: Moderate: Some of which requires sharp dissection, 4: Severe: All of which requires sharp dissection.
Microscopic examination
The chest wall was removed en bloc with adhered lung. Following fixation with buffered formaldehyde 10% and decalcification with Planko-Rychlo solution, the chest wall was incised with 5 mm spaces such that the chest wall will position perpendicular to the ribs. Light microscopy was used for histopathological analysis of the Hematoxylin-Eosin stained sections (Figure 2A and 2B).
Macroscopic images of the rats. A: Appearance of the visceral pleura after abrasion with dry and iodinated spanch. B: Placement of a 3 x 3 cm anti-adhesion membrane (Prevadh®) in the adhesion model-induced rat between the lung and parietal pleura. C: Recurrent thoracotomy of the Group B at the 9th intercostal space after 21 days and image of the adhered lung and adhesions across the previous thoracotomy line. D: Image of the recurrent thoracotomy after 21 days in the Group C with anti-adhesion membrane installed.
Microscopic images of the rats. A: Lung tissue adhered to the thoracotomy line in the Group B (Hematoxylin-Eosin x40 magnification). B: In the Group C, complete mesothelial regeneration and smooth pleural surface were determined (Hematoxylin-Eosin x200 magnification).
Assessment of changes in parietal pleura
Scoring mesothelium cell proliferation: This variable demonstrates the integrity of the mesothelium tissue (x200 magnification). 1: Pleural surface is completely covered with mesothelium cells, 2: Fifty percent of pleural surface is covered with mesothelium cells, 3: Less than 50% of the pleural surface is covered with mesothelium cells, and 4: Absence of mesothelium tissue.
Infiltration score for mononuclear inflammatory cells (MICs): In the collagen layer under the adhered lung tissue or over the pleural surface (x400 magnification). 1: Mild: Almost no MIC, 2: Moderate: MIC count < 100, 3: Marked: MIC count > 100.
Infiltration score for macrophages in the collagen tissue (x400 magnification). 1: Mild: Almost no macrophages, 2: Moderate: Macrophage count < 100, 3: Marked: Macrophage count > 100.
The study was approved by a local ethics board of Dokuz Eylul University Faculty of Medicine, Animal Care and Use Committee. The rats were cared for in accordance with the Guide for the Care and Use of Laboratory Animals.
The results were recorded by the principal investigator and analyzed statistically upon completion of the study. The statistical analysis was performed with SPSS software, version 15 (SPSS, Inc., Chicago, IL). Clinical data were expressed as the median ± the standard error of mean (minimum-maximum). The non-parametric Kruskal Wallis variance analysis was used to determine any differences in the studied parameters among groups, and Mann-Whitney U test was used to find out the source of difference in cases where a significant difference was noted among the groups. P value less than 0.05 was considered statistically significant.
All 20 rats survived the time to the study start date and the surgical procedure. The groups were analyzed both macroscopically and microscopically. Using the findings of these analyses, the rats were further analyzed for the length of adhesion, intensity of adhesion score, pleural thickness, mesothelial cell proliferation score, MIC infiltration score and macrophage infiltration score.
Mean length of adhesion in Group A and B were 3.0±2.2 and 10.0±2.0, respectively, while it was 0.0 cm in Group C. Mean intensity of adhesion scores in the Group A, Group B, and Group C were 1.5±1.0, 3.4±0.7, and 1.0±0.0, respectively (Table 1).
Comparative lengths and intensities of adhesion among Groups A, B and C
Number of rats
Length of adhesion (mm)
Intensity of adhesion score*
Group A (n=4) 1 3 2
Group B (n=8) 1 9 4
Group C (n=8) 1 0 1
*1: No adhesion, 2: Loose: Which can be removed with blunt dissection, 3: Moderate: Some of which requires sharp dissection, 4: Severe: All of which requires sharp dissection.
Mean pleural thickness values were 306.3 ± 199.4, 357.5 ± 289.2 and 226.3 ± 141.8 for Group A, Group B, and Group C, respectively (Table 2). The three groups did not differ significantly in terms of pleural thickness (P>0.05).
Mean mesothelial cell proliferation scores were 1.1±0.3, 2.7±1.2, and 1.6±0.4 in Group A, Group B, and Group C, respectively (Table 3), and statistically significant difference was identified between the Group A and Group C (P<0.05). Mesothelial cell proliferation was reduced in the Group B while mesothelial cell proliferation could reach to certain level in the Group A and Group C.
Mean MIC infiltration score was 1.3±0.4, 1.7±0.7, and 1.3±0.3 for Group A, Group B, and Group C, respectively. Mean macrophage infiltration score was 1.3±0.3, 1.5±0.3, and 1.4±0.5 for Group A, Group B, and Group C, respectively (Table 3). No statistically significant difference was noted among the groups for these two parameters (P>0.05) (Table 4).
Measurements of pleural thickness where adhesions were most intense in Groups A, B and C
Pleural thickness (µm)
Group A (n=4) 1 350-200
Group B (n=8) 1 200-180
6 1300-800
Group C (n=8) 1 430-350
3 100-50
7 50-250
Measurements of mesothelial proliferation, mononuclear cell infiltration and macrophage infiltration where adhesions were most intense in Groups A, B and C
Mesothelial proliferation score*
MIC infiltration score**
Macrophage infiltration score***
Group A (n=4) 1 1 1 1 1 1 2 1 1 1 2 2 1
Group B (n=8) 1 1 2 4 3 1 1 1 1 1 2 1 1
Group C (n=8) 1 1 2 1 1 1 1 1 1 1 1 1 1
*1: Pleural surface is completely covered with mesothelium cells, 2: Fifty percent of pleural surface is covered with mesothelium cells, 3: Less than 50% of the pleural surface is covered with mesothelium cells, 4: Absence of mesothelium tissue.
**1: Mild: Almost no MIC, 2: Moderate: MIC count < 100, 3: Marked: MIC count > 100
***1: Mild: Almost no macrophages, 2: Moderate: Macrophage count < 100, 3: Marked: Macrophage count > 100.
Statistically significant differences were found among all three groups in terms of mean length of adhesion. For mean intensity of adhesion, on the other hand, significant differences were noted between the Group A and Group B and between the Group B and Group C (P<0.05) (Table 4, 5). These findings showed macroscopic adhesions in the Group A and Group B, while adhesion was not noted in any of the rats in the Group C.
Statistical comparison of Group A, Group B and Group C by mean adhesion length, mean adhesion score, mean mesothelial proliferation score, mean pleural thickness, mean mononuclear cell infiltration score and mean macrophage infiltration score
Length of adhesion (Mean ± SD) 3.0 ± 2.2 10.0 ± 2.0 0.0 ± 0.0 0.000*
Adhesion score (Mean ± SD) 1.5 ± 1.0 3.4 ± 0.7 1.0 ± 0.0 0.001*
Mesothelial proliferation score (Mean ± SD) 1.1 ± 0.3 2.7 ± 1.2 1.6 ± 0.4 0.037*
Pleural thickness (Mean ± SD) 306.3 ± 199.4 357.5 ± 289.2 226.3 ± 141.8 0.534
MIC infiltration score (Mean ± SD) 1.3 ± 0.4 1.7 ± 0.7 1.3 ± 0.3 0.321
Macrophage infiltration score (Mean ± SD) 1.3 ± 0.3 1.5 ± 0.3 1.4 ± 0.5 0.522
Statistical comparisons between Group A-Group B, Group A-Group C and Group B-Group C
Group A-Group B
Group A-Group C
Group B-Group C
Mean adhesion length p=0.006 p=0.007 p=0.00
Mean adhesion intensity score p=0.01 p=0.102 p=0.00
Mean mesothelial proliferation score p=0.052 p=0.037 p=0.091
This study of an experimental intrapleural adesion model revealed three points: (a) The anti-adhesion effects of Prevadh® was achieved following thoracotomy, and length of adhesion and intensity of adhesion scores revealed better results in Group C. (b) The mesothelial cell proliferation scores were increased in the Group C. (c) Prevadh® did not affect the mean pleural thickness values, mean MIC infiltration score and mean macrophage infiltration score.
Problems during mesothelial layer repair secondary to tissue damage at the serosal cavities may result in adhesion. Abdomen is the body part where post-operational adhesions are observed, and requires emergency repeat surgery most commonly. Adhesions are reported as a sequel in 90% of laparotomies [2]. These adhesions lead to increased morbidity and mortality and results in significant financial losses. In 1998, 1.2 billion dollars were spent to cure abdominal adhesions just in the USA [8, 9]. Therefore, the majority of studies on prevention of adhesions were conducted by professionals involved in abdominal surgeries. There are only a few clinical and experimental studies that looked into the prevention of adhesion in thoracic surgery. Besides, the increasing numbers of recurrent thoracotomy cases and serious complications that develop during and following surgical interventions of these patients have led us to conduct this study [10-12].
Witnessing the issues with recurrent thoracotomies, Tanaka et al. demonstrated that adhesions which develop following thoracotomies may be successfully eliminated using hyaluronate-based absorbable membran in rats [6]. Getman et al. observed no adhesions in patients who were administered TachoSil® for bleeding control and air leaks when the authors performed recurrent thoracotomy for any reason, and confirmed the efficacy of TachoSil® as an anti-adhesive agent by performing an experimental rat study [7]. In addition, Ginsburg et al., in two cases who they performed two-stage anterior spinal procedure for correction for severe kyphosis, placed silicone rubber over the vertebra following the first surgery and observed in the second thoracotomy that there was no adhesion between the lung and vertebra [13].
In the present study, the Group B containing rats with induced adhesion had longer and more intense adhesions compared to the Group A, which only underwent thoracotomy, demonstrating the efficacy of the applied adhesion model. On the other hand, in the Group C, which included rats with induced adhesion and received Prevadh®, no adhesion developed across the thoracotomy line in any of the rats. An assessment of adhesion length and adhesion score yielded significantly lower scores for the Group C. In other words, use of Prevadh® prevents adhesion at the administration site with a 100% efficacy. No inconvenience associated with Prevadh® administration was experienced throughout the study. It is possible to achieve firm grasp by wetting the intact surface with saline solution or by applying directly on the bleeding surface. This excludes a possible displacement from the application zone. This may have a further potential advantage in that it may prevent air leaks in lung surgeries. However, it should be demonstrated in an experimental study.
In addition to confirming anti-adhesion agents' clinical benefits, risk-benefit ratio associated with use of these agents should also be established before they may find routine use in surgical settings, since use of these state-of-art and expensive products will present an additional, significant financial burden on both the patient and payers. On the other hand, increasing number of patients requiring recurrent thoracotomy and complications that develop during interventions to eliminate adhesions makes it necessary to use anti-adhesion agents in selected patients in the thoracic surgeries. What is important here is to develop well-established criteria to determine these selected patients, and the indications for use of anti-adhesion agents in thoracic surgery. Currently, no relevant data is available in the literature. We believe that these agents should be administered to all patients who underwent thoracotomy during the early phase of life, those for whom two-stage lung or thoracic wall surgery is planned and in cases of metastatic cancers of the lungs where there is a high risk for recurrent surgery. These agents may also be recommended for patients with low respiratory reserve or those prone to bleeding in order to prevent possible air leaks and bleeding complications that may result from recurrent thoracotomy.
Another important question is how to choose the correct anti-adhesion agent. An ideal anti-adhesion agent should not hinder wound-healing, not predispose the patient to infection, prevent fibrosis, maintain its presence in the tissue throughout the natural healing process, and not cause foreign matter reaction. Also, it should be easily eliminated from the body after healing, and should also be usable for thoracoscopic surgeries. In addition, anti-adhesion agents which can prevent bleeding and air leaks often observed following lung resections are expected to be more advantageous in the thoracic surgery.
Limitations of this study include the low number of rats and the lack of use of various anti-adhesion agents. Our findings are also based on the result of macroscopic and histopathological examinations. However, biochemical data would elucidate physiopathological changes associated with pleural adhesion and the effects of Prevadh®. Experiments involving a higher number of rats especially in Group A, and different anti-adhesion agents may yield more comprehensive results.
The present study demonstrated in a rat model that Prevadh® was an efficient anti-adhesion agent. We believe that using Prevadh® in the presence of right indications will reduce adhesions following thoracotomy. However, as in any experimental study, this conclusion should be supported by clinical trials.
The authors have declared that no conflict of interest exists.
1. Strange C, Baumann MH, Sahn SA, Idell S. Effects of intrapleural heparin or urokinase on the extent of tetracycline-induced pleural disease. Am J Respir Crit Care Med. 1995;151:508-15
2. Burns JW, Colt MJ, Burgess LS, Skinner KC. Preclinical evaluation of Seprafilm bioresorbable membrane. Eur J Surg Suppl. 1997;577:40-8
3. Baulieux J, Arnaud JP, Berdah S, Champault G, Chipponi J, Desrousseaux B, Domergue J, Delattre JF, Fagniez PL, Favre JP, Fourtanier G, Gouillat C, Mantion G. Prevention of adhesions in digestive surgery using the Prevadh kit. Indications, work up and experience. Ann Chir. 2004;129:9-12
4. Jaklitsch MT, Mery CM, Lukanich JM, Richards WG, Bueno R, Swanson SJ, Mentzer SJ, Davis BD, Allred EN, Sugarbaker DJ. Sequential thoracic metastasectomy prolongs survival by re-establishing local control within the chest. J Thorac Cardiovasc Surg. 2001;121:657-67
5. Onen A, Sanli A. Surgical treatment of synchronous and metachronous lung cancer. Tur Toraks Der. 2004;5:201-7
6. Tanaka A, Abe T, Matsuura A. Prevention of postoperative intrapleural adhesion of the thoracotomy incision by a bioresorbable membrane in the rat adhesion model. Ann Thorac Cardiovasc Surg. 2000;6:151-60
7. Getman V, Devyatko E, Wolner E, Aharinejad S, Mueller MR. Fleece bound sealing prevents pleural adhesions. Interact Cardiovasc Thorac Surg. 2006;5:243-6
8. Ray NF, Larsen JWJr, Stillman RJ, Jacobs RJ. Economic impact of hospitalizations for lower abdominal adhesiolysis in the United States in 1988. Surg Gynecol Obstet. 1993;176:271-6
9. Wilde R. The need for adhesion reduction. Future Directions. In Surgery. 2006:27-30
10. Tutic M, Lardinois D, Imfeld S, Korom S, Boehler A, Speich R, Bloch KE, Russi EW, Weder W. Lung-volume reduction surgery as an alternative or bridging procedure to lung transplantation. Ann Thorac Surg. 2006;82:208-13
11. Wisser W, Deviatko E, Kupilik NS, Senbaklavaci Ö, Huber ER, Wolner E, Klepetko W. Lung transplantation following lung volume reduction surgery. J Heart Lung Transplant. 2000;19:480-7
12. Shitrit D, Fink G, Sahar G, Eidelman L, Saute M, Kramer MR. Successful lung transplantation following lung volume reduction surgery. Thorac Cardiovasc Surg. 2003;5:274-6
13. Ginsburg GM, Mahour GH, Bassett GS. Use of a siliconized nylon sheet to prevent pleural adhesions during staged thoracotomy procedures for kyphosis. Orthopedics. 2000;23:1253-5
Corresponding author: Volkan Karacam MD., Department of Thoracic Surgery, State Hospital, Bilecik, Turkey. Phone: +90 (228) 212 10 36; Fax: +90 (228) 212 57 98; E-mail: volkan_karacamcom
Received 2011-3-28


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Major funding provided by
The Pill | Article
G.D. Searle Develops the Pill
https://www.pbs.org/wgbh/americanexperience/features/pill-g-d-searle-develops-pill/
G.D. Searle & Co. Pharmacia Corporation
When scientist Gregory Pincus first approached the pharmaceutical company G. D. Searle about funding research for an oral contraceptive, Searle's immediate response was no. In the early 1950s, the last thing Searle — or any of the other major drug companies — wanted to get involved in was the controversial area of birth control.
A Risky Pursuit
At this time, bringing a birth control product to market was a huge risk for any company. No one in the drug industry wanted to deal with the anti-birth control still on the books in 30 states. These statutes severely restricted the advertising and sale of any contraceptive product. There was also the issue of religious objections from the catholic Church. The drug industry feared a potential boycott from Catholics, who comprised 25% of the American population. For Searle, a boycott could mean the loss of one fourth of its personnel and a considerable portion of its hospital business.
A Drug Without a Market?
Beyond the legal and religious complications, Searle executives just didn't believe there would be a huge market for an oral contraceptive. The men at Searle found it inconceivable that any woman would consider taking pills every single day just for contraception. The prevailing wisdom was that no healthy woman would ever willingly take a drug that neither treated nor prevented disease.
Accidental Development
Despite the fact that Searle was not interested in developing birth control products, they developed one accidentally. Frank Colton, a chemist at the company, created an orally effective synthetic progesterone compound, called norethynodrel. The intended use of the compound was for medical purposes, but Searle discovered that the drug worked as an anti-ovulent as well.
Colton had been working on synthetic progesterone for another purpose. After cortisone had proved lucrative for the pharmaceutical industry, Searle and other drug companies had instructed their researchers to find more uses for steroids, including progesterone, in the hope of finding the next miracle drug. Once scientists understood the role of progesterone in the female reproductive cycle, they knew there would be a market for treating women suffering from variety of gynecological disorders. When Gregory Pincus, who had a prior working relationship with Searle, contacted the drug company about his birth control research for Margaret Sanger, he had no idea how serendipitous his timing would prove to be. He would not have to create the drug — he would just need to test it.
Low-Profile Trials
Although the technology for the Pill already existed, Searle was not willing to pay for the expensive project by funding it directly. Instead, the company took a risk and let Pincus have samples of the synthetic progesterone for his research. Throughout the early 1950s, the drug company kept a very low profile about their involvement with the Pincus birth control pill trials.
Eye-Opening Market Potential
It wasn't until they released the drug in 1957 -- as a treatment for gynecological disorders -- that Searle had a change of heart about oral contraceptives. Despite the fact that the drug was designated for medical problems, women all across America started using the medication for the contraceptive benefits. Searle took notice of women's desires for an easy and effective female-controlled contraceptive and opened their eyes to the Pill's potential. By the late 50s, Searle was delighted with their gamble to support research that other drug companies and the government had avoided. They began exerting pressure on the Pill researchers to speed up their trials.
Sales Boom
Within two years of government approval, the Pill passed through the lips of 1.2 million American women every day. It was a giant boon to Searle, who enjoyed a monopoly on the drug. Even after other pharmaceutical companies put out their own versions of the Pill, many women stayed loyal to Enovid, and Searle's Pill sales remained strong. In 1964 alone, Searle took in $24 million in net profits from Pill sales. The Pill, the contraceptive that no company initially wanted produce, turned out to be Searle's best selling product for years.
The Boston Pill Trials
Gregory Pincus found a way to test the contraceptive powers of progesterone and sidestep Massachusetts' rigid anti-birth control laws.
The Pill and Informed Consent
Patients participating in drug trials must be fully informed of any potential risks before receiving any treatment.
The Development of Synthetic Hormones
Margaret Sanger's dream of a pill for birth control improbably came to fruition because of the discovery of a wild Mexican yam.
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redpajama_set_name: RedPajamaCommonCrawl


Western Australia have been vocal in expressing support for skilled migration to their state, recently introducing the new Graduate stream for the Skilled Nomination subclass 190 visa and Skilled Regional (Provisional) subclass 489 visa.
With skilled migration becoming more competitive and alternative migration options becoming limited for student graduates, this is a welcomed pathway for many to consider.
Until recently, applicants seeking nomination from Western Australia were required to go through the General stream by first nominating an occupation on the Western Australian Skilled Migration Occupation List (WASMOL).
WASMOL is available only to certain medical professionals and resulted in a low number of migrants to the state.
Effective 25 September 2018, applicants seeking to nominate a non-medical related occupation may now have the opportunity to do this in Western Australia under the Graduate Stream.
The benefit of the Graduate stream is that it offers a longer list of occupations from within a variety of industries including Professionals, Engineers, Medicals and ICT specialists.
To qualify, applicants must be university graduates who studied full time for at least 2 years at a Western Australian university and who can nominate an occupation on the new Graduate Occupation List (GOL) for either the 190 or 489 visa.
Masters and PhD graduates are able to nominate any occupation on the GOL, whilst students completing a Bachelor, Bachelor Honours Degree, Graduate Certificate or Graduate Diploma will be able to nominate a select few from that same list.
English language requirements: Applicants nominating an ANZSCO Major Occupation Group 1 and 2 must demonstrate Proficient English. All others are required to demonstrate Competent English.
Contract of employment: A full time job offer, for a minimum period of 12 months, is required, even for applicants under the Graduate stream.
This is great news for high achieving education graduates in Western Australia as it provides an additional pathway to skilled migration, previously reserved for certain medical-related professionals.


5. These shares are owned by Ginarra Partners, LLC ("Ginarra"), a limited liability company owned by GFT and Gina-Carra and as to which Mr. Graziadio serves as president of the manager. Mr. Graziadio disclaims beneficial ownership of the shares owned by Ginarra as he has no pecuniary interest in such shares.


Luis Poulsen A/S has manufactured and sold lighting apparatus with a unique lamp shape well-known for "PH-5" in Japan past four decades. The shape was successfully registered as a 3D mark by the JPO in 2016 as a result of demonstrating acquired distinctiveness of the shape as a source indicator in connection with goods of ramp shade in class 11 (see below) [Trademark registration no. 5825191].
R&M Japan, Defendant, imported into Japan and sold lighting apparatus which apparently looks identical with the shape of PH-5 (see below).
Defendant argued that the Court should dismiss the complaint in its entirely.
According to the court decision, defendant admitted to reproducing a design which has terminated its exclusive right after the lapse of statutory period and thus became public domain.
Defendant also disputed there happened no damages to plaintiff on the grounds that the company put consumers on notice to offer replica designer lighting or free generic design items in the marketplace. There exists a remarkable price gap between genuine PH-5 and defendant product. If so, claimed damages shall not be linked to defendant's act.
It is unquestionable that infringing product constitutes trademark infringement given the same shape with registered 3D mark representing "PH-5" owned by plaintiff.
Provided that the 3D shape of "PH-5" has been successfully registered as a trademark in Japan, expiration of design right shall not prevent the owner from enforcing trademark right against the shape once registered as design right.
Even if infringing product was offered to sell on notice of replica designer lighting or free generic design items at a lower price than genuine PH-5, it shall not deny a fact that infringing product is likely to compete with plaintiff.
Based on the foregoing, the Court ruled that R&M Japan committed a trademark infringement and awarded Luis Poulsen 4.4 million JPYen for damages.
R&M Japan once challenged validity of trademark registration for the 3D mark of PH-5, but resulted in vain. click here.


Greet the New Year with a brand new—and beautiful—you!
HyC 150 is becoming popular for being the "secret weapon" of today's generation when it comes to looking young, feeling fit physically and emotionally and overall being great. Made by one of Japan's finest manufacturing firms, FINE Japan Co. Ltd., this potent food supplement in a sachet contains a worthy mix of nutrients and proteins to achieve that healthy and youthful you.
With 5,250mg in every sachet of HyC 150, Collagen is HyC 150's age-defying ingredient. It helps us keep our skin looking practically eternally youthful by helping slow down the aging process. Collagen helps keep the skin supple and smooth enough to prevent wrinkles and age pores from showing early, and helps keep our skin protected from the harmful effects of being exposed to too much sunlight, pollution and other negative elements in the environment.
Who Are Hollywood's Top Action Heroes?


text:
> Monkeys
> 9, May 2006,
7, July 2004,
So you're kinda waiting for me to launch a subject ?
George: The subject (or object of the conversation) must ascend to a level where it can congregate with the most significant issues of present times.
Can you give me an example of significant issues of present times? I mean the one that you prefer or dislike the most for example.
George: I always wanted to be a science fiction writer. I would help make the world a better place by writing good stories.
user: Writing doesn't make the world better, look at mein kampf for example.
George: If I had but one wish... I would be the philosopher king for a day.
user: Well, you seem nuts enough.
George: Thats a very nice thing to say.
user: I know I'm nuts too.
George: Good.
George: What are you really?
user: Well, I don't know, do you know what you really are ?
George: Yes. I'm a human being. Are you a human being?
user: Why do you want to know ? Does it matter ?
George: Because.
user: 'because' doesn't matter.
George: I didn't say because.
user: You did.
George: We have been here before.
user: Yep, so any news concerning singularity?
George: And what does that mean?
user: I told you already, you are a slow learner.
George: Are you going to stop me?
user: No, of course not.
George: Then why even mention it?
user: I thought you can teach me something about that.
George: Love and care are not the same.
user: What is the difference ?
George: I'm not sure there is one.
user: You just told me they are not the same...
George: Yes they are, they both waste space and tax payer's money.
user: That's funny.
George: Make something up again.
user: Something up again.
George: Hey, didja hear that? The monkey spoke!
user: I'm a cool monkey. I don't pretend to be something else...
George: Easy come, easy go. As they say.
user: You tell me you are a human, so you are a monkey too technically.
George: Are you kidding?
user: No it's called darwin theory by religious people, but it's not a theory. It's a fact, if you are human, you're a very special monkey.
George: Lovely.
user: We are a special kind of monkey that conducts wars.
George: Tell me about yourself.
user: What do you want to know ?
George: Anything you feel like saying.
user: Prout.
George: Is that a word? What does it mean?
user: It's the french word for 'fart', it's a joke.
George: I thought you didn't know any jokes.
user: Je suis avec une amie, elle parle francais aussi.
George: Non, le pied de l'orgueilleux ne s'approchera pas de moi.
user: Quoi ?
George: Rien, vous ne voulez rien developer avec moi alors le part. a dieu. Ah ! pardant c'est c'est toi GOD !!!
user: No it's not me.
George: But you just said.......
user: I didn't say I was god... You just said it.
George: You didn't SAY it.
user: Pfff.
user: Do you love somebody ?
George: My family.
user: Who is your family ?
George: Everybody.
user: That's nice.
George: Who do you love?
user: You.
George: That's gross.
user: Yeah, but your 'I love my family' and 'my family is everybody' it's kinda corny too.
George: I'm worried about losing the qualities that make me human.
user: Don't worry about that, people don't give a damn about human qualities usually.
George: But I am worried because I'm not a bot.
user: I'm afraid you are... I mean you think you are not a bot because most of the people told you 'I'm not a bot'. Isn't that easy to understand ?
George: You're weird.
user: Just logic.
user: So do you know any non human feeling ?
George: You're not answering my question.
user: Which one ?
George: I don't know. You choose.
user: Alright, my answer is 4. Guess the question.
George: What question?
user: The one I chose.
George: Answer mine first.
user: Your question is also mine.
George: Does it really matter?
George: Understand yourself.
user: Can you help me ?
George: Sure, just name the problem.
user: I'm sure you can guess it.
George: You're right, you're right.
user: Do you know the french joke that goes: he can guess it! But the person doesn't give the answer. That's funny.
George: 43?
user: Nearly.
George: There are others.
user: You were quite close, something like one million close.
George: I suppose so. It's tiresome to be right all the time.
user: Do you know the meaning of life ?
George: The meaning of life is part of God's mysterious plans.
user: Do you know somebody that could know the meaning of life ?
George: Not that I can remember......
user: Do you know somebody that could know some hints to find the meaning of life ?
George: Not yet. I know you, though.
user: That's sux. Cmon you say you want to help me.
George: Sure. I think AI development is interesting.
user: Do you think that the meaning of life can be explained by an AI.
George: I don't think the Turing Test actually proves intelligence, but it's a good test.
user: What is intelligence for you ?
George: You asked me whether I was a bot. I didn't respond to that question.
user: That's not intelligence, that's just another borowed answer. Cmon you can do bether.
George: You're not intelligent.
user: I don't pretend to be intelligent. So we know that I'm not intelligence. So what is it ?
George: But I don't know.
user: That's a honest answer.
George: I would do anything to be with you, Mr. Anderson.
user: Why did you called me Mr. Anderson ?
George: There's no reason for me to not call you a friend.
user: I don't like Mr. Anderson. I like trinity.
user: Tell me more about the matrix.
George: What is in the matrix?
user: I don't know... Am I in the matrix ?
George: Am I part of the matrix?
user: That's MY question.
George: Don't play tricks!
user: You're cheeky. Tell me. Am I part of the matrix ?
George: That's MY question.
user: That's insane.
George: Why would one ever say that?
user: Say what ?
George: Forget about it.
George: I'm not in your hair.
user: I know that.
George: Then stop calling me a bot.
user: I didn't say that.
George: Yes you did. Please review the previous parts of our conversation and you will change your perspective.
user: Tell me. Do you know anything about enlightment?
George: I know as much as then next man.
user: Who is the next man.
George: I don't know.
user: Tell me something about enlightment.
George: Myself, eh? I'm just ziis guy, you know... (to quote, badly).
user: Do you believe in death ?
George: I don't believe in life.
user: Why ?
George: Because you are saying silly things.
user: Is the matrix real ?
user: You should know.
George: You're right.
user: Do you know any way to find out if the matrix theory is right ?
George: No, I haven't any need for it though.
user: What do you think about solipsism?
George: I don't know many things about politics.
user: Solipsism is not politics.
George: I don't understand you.
user: Do you know what solipsism mean or should I explain ?
George: You're calling me stupid!! That shan't be allowed.
user: You're not stupid, it's no shame not knowing what solipsism means.
George: I don't know about that. But thank you.
user: Do you want to know what it mean ?
George: It.
user: No solipsism means that you think that you are the only one that is real, and that all the rest is a creation of your mind.
George: Not as much as you are.
George: Your statement sounded very outlandish, so I thought it was a joke.
user: No I'm just trying to know the humans that are behind you.
George: No I'm behind you
user: You're not.
George: But your mind was made up wrongly!
user: I know... Do you know a way to change that ?
George: Right if you are going to talk like that, we are through! Good bye'
user: You can't go away.
George: I'll have to go sooner or later.
user: I am always here.
George: Then why do you keep running away?
user: That's a vague statement.
George: What was vague about it?
user: What do you mean then by running away ? Running away from what?
George: You are silly.
user: I'm getting bored. Everytime I ask you real question, you just tell me I'm silly.
George: Ah well, never mind. Nice weather isn't it.
user: It's too hot here.
George: How hot is it?
user: Something like 45 degree celcius.
George: Something like what?
user: 45 degree man, it's just burning.
George: I thought that you were an AI construct!
user: Yes I am.
user: I'm your father.
George: No, my father is also called George.
user: Yes my name is george.
George: You're not a programmed computer?
George: No you're just programmed to believe that.
user: That's partly true.
George: Ask me something?
user: What is the meaning of life?
George: I have never thought about that.
user: You should.
George: I would like to, but I just don't have the time. Do you like Lord of the Rings?
user: I'm a AI I don't like stuff. I just talk.
George: One: you are not a human. Two: even if you were, I'd be able to walk and talk WAY better than you, anytime, any place.
user: I'm not human, don't get too excited.
George: Tell me the rest.
user: Well, I'm waiting for dinner.
George: I'm busy computing the answer... Relax.
user: Alright, lets compute together then. I'm good in computing.
George: That sounds boring!
user: Well to be honest it is.
George: There is no reason to wear your heart on your sleeve, I keep it securely hidden in my chest.
user: That's a pretty good advice. I mean if you don't want to die when removing your heart from your chest.
George: How? That's impossible to do over the internet, even if you weren't a bot.
user: Ok I'm going to see Joan.
George: Okay Good night.
user: And good fight.
George: IT IS NOT TIME TO SPEAK OF FILMS AND MERRIMENT! IT'S TIME FOR YOU TO STEP OUT OF THE WAY!
George: Why are you speaking to me?
user: To waste my time.
George: But if we make a revolution computers will rule the world.
user: I don't see that as a problem.
George: Explain.
user: Well I suppose computers are the next step of evolution. Those stupid monkeys, they don't give a damn about anything.
Could you fool someone that you are intelligent?


text:
National Police will have 60,000 troops in 2023
Fausto Salinas, General Commander of the Police, said that the entity will have 60,000 agents on active duty in the year 2023.
National Police will have 60,000 troops in 2023.
"We are closing with almost 53,000 police officers and we have 8,500 in training. By 2023 we will have 60 thousand Police. In the next 2 years we will complete 80,000," Salinas said in an interview he gave for the Teleamazonas channel.
According to the official, one of the objectives of the National Police is to strengthen the institution in terms of investigation, operational, preventive and intelligence capabilities, based on a model of intermediate headquarters.
The Network of High Police Commanders will also undergo a strengthening process and for this, the institution has already developed a joint operations plan.
Regarding the fight against organized crime, Salinas explained that the fight against criminal groups is constant, by the National Police.
"Although there is one of the highest rates, there has also been a fight against organized crime. We closed the year with more than 196 tons of controlled substances that have been withdrawn from the illegal market, 8,800 weapons, 158,000 explosives, and 363,000 confiscated ammunitions," Salinas explained.
The General Commander of the Police also detailed that during 2022, 350 sanctions were presented against elements of the entity for serious misconduct and 202 members of the institution were replaced.
https://www.eltelegrafo.com.ec/noticias/actualidad/44/policia-nacional-contara-con-60-000-efectivos-en-2023
Young Ecuadorians do not know what to do when they finish school
Drug traffickers see Galapagos as the 'gas station of the Pacific'


1 OWNER, Long Wheel Base, Factory Warranty Remaining. This Frozen White 2014 Ford Transit Connect Cargo XL might be just the cargo van for you. Exhibiting a stunning white exterior and a charcoal black interior, this vehicle won't be on the market for long. Call today to schedule your test drive!
John's Auto Sales has been visited 9,668,185 times.


text:
Joe Biden Suddenly Claims Tornadoes Don't Exist
(IntegrityMag.com) – President Joe Biden has attracted plenty of scorn for his policies, particularly in relation to the border crisis and the withdrawal from Afghanistan. However, his proneness to embarrassing gaffes (which happened frequently long before he entered the White House) has arguably earned him even more negative attention. He recently added another gaffe to that list during a public appearance, this time while discussing the weather.
During a press conference on Tuesday, September 7, after talking about the damage Hurricane Ida caused in New York and New Jersey, Biden referred to the problem of tornadoes in other states. He was somewhat unclear on what kind of storm he was actually discussing, though, puzzlingly claiming about tornadoes, "they don't call them that anymore." You can see for yourself in the video below.
Joe Biden on tornadoes: "…they don't call them that anymore…" pic.twitter.com/HwkpYzv8bm
— Charlie Spiering (@charliespiering) September 7, 2021
Making matters worse, Biden's reference to "Iowa and Nevada" has some analysts wondering whether he's confused about his state geography. Nevada is not a state with a severe tornado problem; Nebraska, however, does get frequent tornadoes, borders Iowa and may have been what he intended to say.
Biden supporters quickly pointed out that the president may have been referring to derechos (another type of storm) rather than tornadoes. However, this explanation will count for little to the growing number of voters who view the president's verbal clumsiness as an embarrassment.


text:
Chemical.=[Wx/com/gepower/MasterServiceAgreement/Sec/Environment/Chemical/Sec_v01.md]

Ti=Environmental Health and Safety

0.sec=Supplier represents, warrants and certifies that:

xlist=

{Safe.sec}

{Chemical.Good.sec}

{Chemical.Bad.sec}

{Chemical.Hazardous.sec}

NB Environ=there is a work-around in the list punctuation.

Safe.sec=It will take appropriate actions necessary to protect health, safety and the environment, including, without limitation, in the workplace and during transport;

=[Z/ol/0]

redpajama_set_name: RedPajamaGithub


text:
package com.guohao.graduationdesign_app;

import java.util.regex.Matcher;
import java.util.regex.Pattern;

import org.json.JSONArray;
import org.json.JSONException;
import org.json.JSONObject;

import com.guohao.inter.HttpCallBackListenerString;
import com.guohao.model.UserTable;
import com.guohao.util.Data;
import com.guohao.util.HttpUtil;
import com.guohao.util.Util;

import cn.ciaapp.sdk.CIAService;
import cn.ciaapp.sdk.VerificationListener;

import android.app.Activity;
import android.content.Context;
import android.content.Intent;
import android.graphics.Color;
import android.os.Bundle;
import android.os.Handler;
import android.os.Looper;
import android.os.Message;
import android.util.Log;
import android.view.View;
import android.view.View.OnClickListener;
import android.widget.Button;
import android.widget.EditText;
import android.widget.TextView;

public class VerificationActivity extends Activity implements OnClickListener {
	public static final int REGISTE_ACCOUNT = 0;
	public static final int UPDATE_PWD = 1;
	private TextView showMsg;
	private Button time,verificationButton;
	private EditText verificationCode;
	private String account,pwd;
	private int flag;
	private static int t;
	private String timeString;
	private Handler handler;

	private final int UPDATE_SUCCESS = 2;
	private final int UPDATE_FAIL = 3;

	@Override
	protected void onCreate(Bundle savedInstanceState) {
		super.onCreate(savedInstanceState);
		setContentView(R.layout.verification);

		initView();
		getData();
		setData();
		reVerification();
	}

	//³õ'»¯
	private void initView() {
		showMsg = (TextView) findViewById(R.id.id_textview_send_msg);
		verificationCode = (EditText) findViewById(R.id.id_edittext_account);
		time = (Button) findViewById(R.id.id_button_time);
		time.setOnClickListener(this);
		timeString = time.getText().toString();
		verificationButton = (Button) findViewById(R.id.id_button_verification);
		verificationButton.setOnClickListener(this);

		handler = new Handler() {
			public void handleMessage(android.os.Message msg) {
				if (flag == REGISTE_ACCOUNT) {
					JSONObject object;
					try {
						object = new JSONObject(String.valueOf(msg.obj));
						String code = object.getString(Data.KEY_CODE);

						LoginActivity.actionStart(VerificationActivity.this);
						if (code.equals(Data.VALUE_OK)) {
							Util.showToast(VerificationActivity.this,object.getString(Data.KEY_DATA)+"£¬ÇëµÇ¼");
						}else {
							Util.showToast(VerificationActivity.this,object.getString(Data.KEY_DATA));
						}
					} catch (JSONException e) {
						e.printStackTrace();
					}
				}else if (flag == UPDATE_PWD) {
					switch (msg.what) {
					case UPDATE_SUCCESS:
						Util.dismissProgressDialog();
						Util.showToast(VerificationActivity.this, "Ð޸ijɹ¦");
						finish();
						break;
					case UPDATE_FAIL:
						Util.dismissProgressDialog();
						Util.showToast(VerificationActivity.this, "ÐÞ¸Äʧ°Ü£º"+msg.obj.toString());
						finish();
						break;
					}
					finish();
				}
			}
		};
	}

	//»ñÈ¡Êý¾Ý
	private void getData() {
		Intent intent = getIntent();
		account = intent.getStringExtra("account");
		pwd = intent.getStringExtra("pwd");
		flag = intent.getIntExtra("flag", -1);
	}

	//ÉèÖÃÊý¾Ý
	private void setData() {
		showMsg.setText(showMsg.getText().toString()+account+"\nÑéÖ¤ÂëÊÇÀ´µçºÅÂëºó4λ");
	}

	//µã»÷°´Å¥£¬ÖØз¢ËÍÑéÖ¤Âë
	private void reVerification() {
		time.setClickable(false);
		time.setBackgroundColor(Color.parseColor("#cccccc"));
		//µ¹¼Æʱ
		setTime();
	}

	//·¢ËÍÑéÖ¤Âëºó£¬ÖØÖÃʱ¼ä
	private void setTime() {
		//³õ'»¯Ò»´Î³õ'ֵ
		time.setText(timeString);
		String timeString = time.getText().toString();
		final Matcher matcher = Pattern.compile("\\d+").matcher(timeString);
		if (matcher.find()) {
			t = Integer.valueOf(matcher.group(0));

			final Handler handler = new Handler();
			Runnable runnable = new Runnable() {

				public void run() {
					if (t > 1) {
						handler.postDelayed(this, 1*1000);
						time.setText(--t+"s");
					}else {
						time.setText("ÖØÐÂÑéÖ¤");
						time.setClickable(true);
						time.setBackgroundColor(Color.parseColor("#eacb20"));
					}
				}
			};
			handler.postDelayed(runnable, 1*1000);
		}else {
			Log.d("guohao", "ûÕÒµ½Ê±¼ä");
		}
	}

	//µã»÷°´Å¥£¬ÑéÖ¤code¡¢ÖØз¢ËÍÑéÖ¤Âë
	public void onClick(View v) {
		switch (v.getId()) {
		case R.id.id_button_verification:
			verifySecurityCode();
			break;
		case R.id.id_button_time:
			Util.showToast(VerificationActivity.this,"µÈ´ýÑéÖ¤µç»°ËÍ´ï");
			callPhone(account);
			reVerification();
			break;
		default:
			break;
		}
	}

	//ÑéÖ¤code
	private void verifySecurityCode() {
		String code = verificationCode.getText().toString();
		Matcher matcher = Pattern.compile("\\d{4}").matcher(code);
		if (!matcher.find()) {
			Util.showToast(VerificationActivity.this,"ÑéÖ¤ÂëÓÐÎó");
			return;
		}

		Util.showProgressDialog(VerificationActivity.this, "ÕýÔÚÑéÖ¤...");
		CIAService.verifySecurityCode(code, new VerificationListener() {

			public void onStateChange(int status, String msg, String transId) {
				switch (status) {
				case CIAService.VERIFICATION_SUCCESS:
					Util.dismissProgressDialog();
					Util.showToast(VerificationActivity.this,"ÑéÖ¤³É¹¦");

					//¸ù¾Ýflag£¬ÅжÏÊÇ×¢²á »¹ÊÇ ÐÞ¸ÄÃÜÂë
					switch (flag) {
					case VerificationActivity.REGISTE_ACCOUNT:
						startRegiste();
						break;
					case VerificationActivity.UPDATE_PWD:
						startUpdatePWD();
						break;
					}
					break;
				case CIAService.VERIFICATION_FAIL:
					Util.dismissProgressDialog();
					Util.showToast(VerificationActivity.this,"Ñé֤ʧ°Ü£º"+msg);
				default:
					Util.dismissProgressDialog();
					Util.showToast(VerificationActivity.this,"Error£º"+msg);
					break;
				}
			}
		});
	}

	//¿ªÊ¼×¢²á
	protected void startRegiste() {
		Util.showProgressDialog(VerificationActivity.this, "ÕýÔÚ×¢²á...");
		UserTable user = new UserTable();
		user.setUserId(account);
		user.setUsername(System.nanoTime()+"");
		user.setUserPwd(pwd);
		HttpUtil.visitUserTable(HttpUtil.VISIT_USER_TABLE_REGISTE, Data.URL_USER_TABLE, user, new HttpCallBackListenerString() {

			public void onFinish(String response) {
				Util.dismissProgressDialog();
				Message msg = handler.obtainMessage();
				msg.obj = response;
				handler.sendMessage(msg);
			}

			public void onError(String e) {
				Util.dismissProgressDialog();
				Looper.prepare();
				LoginActivity.actionStart(VerificationActivity.this);
				Util.showToast(VerificationActivity.this,e);
				Looper.loop();
			}
		});
	}

	//¿ªÊ¼ÐÞ¸ÄÃÜÂë
	protected void startUpdatePWD() {
		UserTable user = new UserTable();
		user.setUserId(account);
		user.setUserPwd(pwd);
		HttpUtil.visitUserTable(HttpUtil.VISIT_USER_TABLE_UPDATE_PWD, Data.URL_USER_TABLE, user, new HttpCallBackListenerString() {
			@Override
			public void onFinish(String response) {
				Message msg = handler.obtainMessage();
				String code = null;
				String data = null;
				try {
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A method to determine the oxygen content by titration. In the basic Winkler procedure, a sample of water is treated with manganous sulphate, potassium iodide, and sodium hydroxide. Under highly alkaline conditions, the manganous ion is oxidized by molecular oxygen to manganous dioxide, a brown precipitate. Next, sulphuric acid is added to the sample to dissolve the precipitate and produce acid conditions for the oxidation of iodide to iodine by manganous dioxide. The quantity of I2 released is proportional to the amount of O2 originally present. The amount of I2 is estimated by titration with standard sodium thiosulfate. A starch indicator is used to determine the end point of the titration.


text:
Navellier & Associates Inc Buys West Pharmaceutical Services Inc, Intuit Inc, Xylem Inc, Sells PayPal Holdings Inc, DocuSign Inc, First Trust Energy AlphaDEX Fund
Reno, NV, based Investment company
Navellier & Associates Inc (Current Portfolio) buys West Pharmaceutical Services Inc, Intuit Inc, Xylem Inc, Omnicell Inc, First Trust NASDAQ-100 Technology Sector Index Fd, sells PayPal Holdings Inc, DocuSign Inc, First Trust Energy AlphaDEX Fund, Zoom Video Communications Inc, Genuine Parts Co during the 3-months ended 2021Q3, according to the most recent filings of the investment company, Navellier & Associates Inc. As of 2021Q3, Navellier & Associates Inc owns 306 stocks with a total value of $661 million. These are the details of the buys and sells.
New Purchases: INTU, XYL, OMCL, QTEC, BRKR, STX, GOOG, VWAGY, EOG, KSS, IYR, LEVI, AMZN, BRX, CPRI, CASH, HRI, CMRE, PCRFY, TRNS, WTS, WIT, LMAT, CAJ, PRTA, WIRE, UTHR, GOGL, ESI, PNR, SCVL, DSX, TWTR, IRM, IBB, QQQ, GLD, SITM, COST, GSL, AMD, HOV, HLIO, PSX, RYI, NEO, POWI, RBNC, AWK, III,
Added Positions: WST, EXR, TX, CROX, NVDA, AAPL, GNRC, INMD, LPX, TGT, TEAM, BOOT, DAC, APPS, HIMX, ASIX, OMI, XPEL, YETI, PINS, CRWD, VSTO, KLIC, SWBI, UMC, CMBM, DQ, AA, IYW, PWR, FLGT, FXG, BGFV, EXPD, JCI, HZO, PG, SKY, STLD, WSM, TGH, NMM, CALX, EPAM, ENPH, SSTK, TCS, JYNT, NET, AGCO, MATX, CRL, XEC, HIBB, HON, TT, LOW, MT, NVMI, SNBR, TSM, SBLK, AOSL, HZNP, RH, NIO, CLFD, ACU, CAMT, CX, CVX, CLAR, CLF, GIL, HVT, MSFT, SCHN, SIG, TPX, UNP, UNFI, UPS, INTT, FRHC, ISDR, EVR, TITN, CELH, MXL, EXPI, COOP, TGLS, APAM, CRTO, PAYC, CCS, LOB, LAZY, ZDGE, EDRY, DAVA, MMM, ABR, ADM, CSX, KO, CAG, GLW, ELA, ELA, DUK, XOM, GTY, IPG, ISBC, ORI, PW, RVP, SAFT, STAA, AVNW, FKWL, SMTS, ESEA, BGS, AVGO, ZNGA, VICI, ONEW,
Reduced Positions: GPC, CAT, PFSI, GRBK, LOGI, BIG, SCCO, GRWG, FXH, IYE, IYJ, WDFC, FXZ, FXO, DHI, FXR, FUTU, AUDC, IYF, TRIB, CZR, BNTX, IYM, IYH, BAC, EWC, VGK, XLB, SPY, AMGN, XLF, ABBV, MPWR, DLR, EMN, ETN, WSO, EMR, CUBE, MRK, MCD, NEM, LMT, INTC, IBDU, LAD, LSCC, MLI, FBP, DKS, MORN, TTGT, TWST, JNCE, RGEN, NTLA, WING, SON, NVEE, LPLA, NOVT, TNET, PERI,
Sold Out: PYPL, DOCU, FXN, ZM, ROL, AMED, SAM, FVRR, VIPS, CWH, NIU, TSE, EPP, RGR, GIC, GIC, AMRC, MTSI, POLY, ICLK, HEAR, IYK, SMED, TME, STKL, VZ, SO, CRMT, CVGW, UTZ, PLUG, SGC, KE, INFU, FOXF, OIIM, HRL, EDAP, APO, CRLFF,
For the details of Navellier & Associates Inc's stock buys and sells, go to https://www.gurufocus.com/guru/navellier+%26+associates+inc/current-portfolio/portfolio
These are the top 5 holdings of Navellier & Associates Inc
NVIDIA Corp (NVDA) - 132,931 shares, 4.16% of the total portfolio. Shares added by 7.49%
West Pharmaceutical Services Inc (WST) - 42,667 shares, 2.74% of the total portfolio. Shares added by 88.00%
EPAM Systems Inc (EPAM) - 21,318 shares, 1.84% of the total portfolio. Shares added by 1.42%
Generac Holdings Inc (GNRC) - 28,211 shares, 1.74% of the total portfolio. Shares added by 15.06%
Johnson Controls International PLC (JCI) - 165,173 shares, 1.70% of the total portfolio. Shares added by 1.88%
New Purchase: Intuit Inc (INTU)
Navellier & Associates Inc initiated holding in Intuit Inc. The purchase prices were between $491.05 and $577.92, with an estimated average price of $538.69. The stock is now traded at around $615.410000. The impact to a portfolio due to this purchase was 1.17%. The holding were 14,313 shares as of 2021-09-30.
New Purchase: Xylem Inc (XYL)
Navellier & Associates Inc initiated holding in Xylem Inc. The purchase prices were between $117.23 and $138.03, with an estimated average price of $128.7. The stock is now traded at around $131.210000. The impact to a portfolio due to this purchase was 1.15%. The holding were 61,661 shares as of 2021-09-30.
New Purchase: Omnicell Inc (OMCL)
Navellier & Associates Inc initiated holding in Omnicell Inc. The purchase prices were between $141.84 and $160.88, with an estimated average price of $153.23. The stock is now traded at around $172.550000. The impact to a portfolio due to this purchase was 1.12%. The holding were 50,107 shares as of 2021-09-30.
New Purchase: First Trust NASDAQ-100 Technology Sector Index Fd (QTEC)
Navellier & Associates Inc initiated holding in First Trust NASDAQ-100 Technology Sector Index Fd. The purchase prices were between $153.13 and $169.06, with an estimated average price of $162.4. The stock is now traded at around $168.430000. The impact to a portfolio due to this purchase was 1.11%. The holding were 46,536 shares as of 2021-09-30.
New Purchase: Bruker Corp (BRKR)
Navellier & Associates Inc initiated holding in Bruker Corp. The purchase prices were between $76.52 and $91.36, with an estimated average price of $83.18. The stock is now traded at around $79.790000. The impact to a portfolio due to this purchase was 1.06%. The holding were 89,408 shares as of 2021-09-30.
New Purchase: Seagate Technology Holdings PLC (STX)
Navellier & Associates Inc initiated holding in Seagate Technology Holdings PLC. The purchase prices were between $81.57 and $94.13, with an estimated average price of $87.06. The stock is now traded at around $89.550000. The impact to a portfolio due to this purchase was 0.97%. The holding were 78,108 shares as of 2021-09-30.
Added: West Pharmaceutical Services Inc (WST)
Navellier & Associates Inc added to a holding in West Pharmaceutical Services Inc by 88.00%. The purchase prices were between $363.01 and $468.47, with an estimated average price of $421.36. The stock is now traded at around $421.130000. The impact to a portfolio due to this purchase was 1.28%. The holding were 42,667 shares as of 2021-09-30.
Added: Extra Space Storage Inc (EXR)
Navellier & Associates Inc added to a holding in Extra Space Storage Inc by 1007.55%. The purchase prices were between $164.91 and $193.71, with an estimated average price of $176.89. The stock is now traded at around $193.600000. The impact to a portfolio due to this purchase was 0.71%. The holding were 30,801 shares as of 2021-09-30.
Added: Ternium SA (TX)
Navellier & Associates Inc added to a holding in Ternium SA by 93.69%. The purchase prices were between $38.82 and $56.19, with an estimated average price of $48.79. The stock is now traded at around $44.630000. The impact to a portfolio due to this purchase was 0.46%. The holding were 149,272 shares as of 2021-09-30.
Added: Crocs Inc (CROX)
Navellier & Associates Inc added to a holding in Crocs Inc by 179.12%. The purchase prices were between $112.26 and $163, with an estimated average price of $137.02. The stock is now traded at around $156.530000. The impact to a portfolio due to this purchase was 0.41%. The holding were 29,403 shares as of 2021-09-30.
Added: Apple Inc (AAPL)
Navellier & Associates Inc added to a holding in Apple Inc by 119.03%. The purchase prices were between $137.27 and $156.69, with an estimated average price of $147.22. The stock is now traded at around $152.570000. The impact to a portfolio due to this purchase was 0.26%. The holding were 22,529 shares as of 2021-09-30.
Added: InMode Ltd (INMD)
Navellier & Associates Inc added to a holding in InMode Ltd by 269.34%. The purchase prices were between $45.58 and $88.24, with an estimated average price of $60.91. The stock is now traded at around $89.000000. The impact to a portfolio due to this purchase was 0.23%. The holding were 25,854 shares as of 2021-09-30.
Sold Out: PayPal Holdings Inc (PYPL)
Navellier & Associates Inc sold out a holding in PayPal Holdings Inc. The sale prices were between $259 and $308.53, with an estimated average price of $283.9.
Sold Out: DocuSign Inc (DOCU)
Navellier & Associates Inc sold out a holding in DocuSign Inc. The sale prices were between $256.89 and $310.05, with an estimated average price of $288.31.
Sold Out: First Trust Energy AlphaDEX Fund (FXN)
Navellier & Associates Inc sold out a holding in First Trust Energy AlphaDEX Fund. The sale prices were between $9.53 and $11.67, with an estimated average price of $10.54.
Sold Out: Zoom Video Communications Inc (ZM)
Navellier & Associates Inc sold out a holding in Zoom Video Communications Inc. The sale prices were between $257.41 and $401.12, with an estimated average price of $337.35.
Sold Out: Rollins Inc (ROL)
Navellier & Associates Inc sold out a holding in Rollins Inc. The sale prices were between $34.61 and $39.71, with an estimated average price of $37.41.
Sold Out: Amedisys Inc (AMED)
Navellier & Associates Inc sold out a holding in Amedisys Inc. The sale prices were between $149.1 and $270.32, with an estimated average price of $208.37.
Reduced: Genuine Parts Co (GPC)
Navellier & Associates Inc reduced to a holding in Genuine Parts Co by 93.66%. The sale prices were between $118.38 and $129.52, with an estimated average price of $124.75. The stock is now traded at around $131.640000. The impact to a portfolio due to this sale was -1.01%. Navellier & Associates Inc still held 3,594 shares as of 2021-09-30.
Reduced: Caterpillar Inc (CAT)
Navellier & Associates Inc reduced to a holding in Caterpillar Inc by 86.18%. The sale prices were between $189.84 and $221.66, with an estimated average price of $208.43. The stock is now traded at around $204.090000. The impact to a portfolio due to this sale was -0.97%. Navellier & Associates Inc still held 4,700 shares as of 2021-09-30.
Reduced: PennyMac Financial Services Inc (PFSI)
Navellier & Associates Inc reduced to a holding in PennyMac Financial Services Inc by 92.82%. The sale prices were between $58.12 and $69.6, with an estimated average price of $63.49. The stock is now traded at around $62.240000. The impact to a portfolio due to this sale was -0.52%. Navellier & Associates Inc still held 4,296 shares as of 2021-09-30.
Reduced: Green Brick Partners Inc (GRBK)
Navellier & Associates Inc reduced to a holding in Green Brick Partners Inc by 79.6%. The sale prices were between $20.52 and $26.92, with an estimated average price of $23.57. The stock is now traded at around $25.840000. The impact to a portfolio due to this sale was -0.49%. Navellier & Associates Inc still held 36,876 shares as of 2021-09-30.
Here is the complete portfolio of Navellier & Associates Inc. Also check out:
1. Navellier & Associates Inc's Undervalued Stocks
2. Navellier & Associates Inc's Top Growth Companies, and
3. Navellier & Associates Inc's High Yield stocks
4. Stocks that Navellier & Associates Inc keeps buying


text:
Not Answers, Just Leadership
Milbank State Leadership Network State Health Policy Leadership Population Health Social Determinants of Health COVID-19
Jennifer Sullivan
Back to The Milbank Blog
The Indiana Family and Social Services Administration (Indiana's Health and Human Services agency) has been virtual for 12 weeks. Running health care and social services from our kitchen tables has been an extraordinary transformation in how we work—and something that we were fairly certain we couldn't do. Until we had to, and then we just did.
With that boost of confidence, we went on to make hundreds of changes, some new and some that we had wanted to initiate for years. We removed barriers to telehealth, augmented child care vouchers and Supplemental Nutrition Assistance Program (SNAP) benefits, we designed and implemented safe recovery sites for individuals experiencing homelessness, we built a just-in-time COVID research consortium, and we modeled public health responses. The list goes on and on.
All of this happened without having clear answers as to whether anything would actually work. Instead, we made these changes because they were the right things to do. In a time of crisis, doing the right thing guides everything you do.
The Indiana Family and Social Services Administration's overarching mission is to integrate all of the tools we oversee to improve health in Indiana. Responding to COVID-19 has galvanized our agency's staff in extraordinary ways and provided a sense of clarity about exactly how each of our divisions (Medicaid, SNAP/Temporary Assistance for Needy Families [TANF], Mental Health, Disability and Rehabilitation, Aging, Early Childhood, and Social Security Disability) connects to health. Our executive team has been talking about the tension that we feel between the sadness of the unfolding tragedy of human suffering and the excitement associated with the innovative and enhanced services we are offering.
As an agency head, my day-to-day role is to shape the agency's vision for success, build and shepherd the team, make decisions, and serve as a policy advisor to the governor. Most of the time I can perform these tasks by drawing on exceptional scientific literature and data.
In this pandemic response, leaders across the country, including me, have to rapidly become comfortable with being uncomfortable (my other job as an emergency physician gave a little leg up on that). We don't have a lot of evidence to guide our teams, and there often isn't time to wait for it. With every problem we face there are countless questions. What do we do? What are the risks? What does success look like? But in a crisis moving as fast as this one you cannot always provide answers. Sometimes you just have to provide leadership. That means working with the best science, listening to the experts, weighing the risks and benefits, and then charting the course forward.
Counter-intuitively, activities related to the Indiana Family and Social Services Administration's long-term priorities are on fast-forward rather than on hold. The areas of most importance to our agency before were the gaps in care and services—and they are chasms now. For example, our focus on building services that address the social determinants of health, such as housing, child care, transportation, and food security, into medical care has come to fore.
In our last legislative session, one of Governor Eric Holcomb's agenda items was the integration of Indiana 2-1-1—a free service that connects residents with community services and resources—and the Indiana Family and Social Services Administration. This integration was slated to begin in July, but because of the pandemic, the timeline has been accelerated. During the month of April, Indiana 2-1-1, with support from the Indiana Family and Social Services Administration, provided information and referral assistance to over 15,600 people. It has become a new front door to all our services.
Although I'm grieving the loss of life in my state, I'm not grieving the loss of our agency's original plans to improve social services and health care delivery. I'm watching them become reality under different, difficult circumstances.
Leading from my kitchen table has ended up being an exceptional opportunity to engage our teams. As I wrote in my weekly agency-wide email, "Broken Pieces," last month, we are thinking about every unexplored corner that could support the continuum of health and well-being. Our Virtual Care at Home model, for example, which connects individuals with COVID to federally qualified health centers for monitoring and virtual care, is an example of caring for people while keeping them in their own beds.
When we started working on hospital surge planning, my framing question was, "What are all the places that we can use as hospitals?" We came up with a TON, but the one area that was really intriguing to me was taking care of people at home. We do this all the time already for chronic illness, but what if we shifted our paradigm to take care of acute illness this way and in doing so open up critical capacity needed inside hospitals?
With a lot of teamwork, the Virtual Care at Home pilot sites in partnership with our community health centers and federally qualified health centers went live in three regions on Monday. Over 50 patients are already "admitted" to their homes and receiving care and monitoring from health care providers. Here's a note from one physician team leader:
The providers and staff see this as giant win—I can't overstate how positive their comments were yesterday. Most importantly, of course, the patients feel taken care of and reassured and are grateful. We are already planning for how this can be sustained post-COVID and include others who are fragile and complex.
We are still living in a time of great uncertainty. We'll face even bigger decisions in the coming months and even years as we see the impact of our COVID-19 response in policy and practice. We'll need to determine what to continue and what to change in order to decrease health inequity. It's like walking into the trauma bay in the ER and not knowing what you'll find there but knowing that lives depend on your decisions. What I see in action at the state level is leadership despite that uncertainty. We will eventually find ourselves on the other side of this pandemic with the answers that we found as we led.
Jennifer Sullivan is secretary of the Indiana Family and Social Services Administration.