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However medicine 377 order lumigan on line amex, there is only a limited than infants of mothers who did not seroconvert during pregnancy (5 understanding of the evolution of the human antibody response at the [45%] of 11 vs treatment without admission is known as discount lumigan 3 ml amex. To address this problem medications memory loss generic 3 ml lumigan mastercard, we recruited travelers the initial epidemic in early 2015 medicine 6469 purchase lumigan 3 ml with mastercard. Main underlying causes in children of Oxford, Oxford, United Kingdom, 3Lancaster University, Lancaster, 1-59 mos old (n=101) were lower respiratory infections (16), malnutrition United Kingdom (12), congenital birth defects (12), neonatal preterm birth complications (11), and diarrheal diseases (9). Pathogens contributed to death in We present fndings from an effort to produce high resolution maps 58% of cases; 31% had multiple causal pathogens. Leading pathogens of mortality rates and death counts for neonates, infants, and children were Klebsiella pneumoniae, Acinetobacter baumannii, Streptococcus under-5 across 120 low and middle income countries. Among 49 preterm cases, We compiled and geo-referenced data on nearly 28 million child deaths 36 (73%) had >1 pathogen in the causal chain. Sources include complete and transport, poisoning) and noncommunicable conditions (sickle cell, cancer) summary birth histories from sample surveys and censuses, in combination were also observed. We developed these early data highlight the importance of understanding multicausal new methods to account for biases in these various data sources across patterns, maternal factors, and interplay between infectious and chronic space and time, including systematic under-reporting in vital registration conditions in child deaths. We focus specifcally on subnational heterogeneity in the 1427 proportion of child deaths in different age groups under 5. Finally, in addition maps of mortality rates, we also provide estimates of numbers of Allan W. Swanson2, Navit Salzberg3, Pratima child deaths by 5x5 pixel and by subnational units (districts and provinces). Madhi4, Richard Chawana4, Inacio Such maps will arm policymakers with information critical in targeting Mandomando5, Quique Bassat6, Samba Sow7, Karen L. Surveillance deaths in this at-risk group would require delivery by more highly skilled for under-5 deaths and stillbirths began in one site in December 2016, medical personnel. As of February, 2018, 5 sites (Manhica, Mozambique; Soweto, South Africa; Bamako, 1429 Mali; Kisumu, Kenya; Baliakandi, Bangladesh) were actively collecting mortality surveillance and laboratory data. Screening determined 1074 cases 1 2 3 4 (42% of unique notifcations) to be eligible for inclusion. Of all eligible deaths, 707 (66%) were notifed within 24 hours of death (23% over 24 hours; 11% missing), with this proportion Trust, Nairobi, Kenya increasing from 47% in Dec 2016 to 75% in January, 2018. The performance of these models may be evaluated further by 2015-June 2016, a cohort study was implemented in 5 health facilities geographical external validation using data from similar neonatal units in rural Niger (Zinder region, Mirriah department), enrolling all pregnant followed by impact assessment in a cluster randomised controlled trial. We used a 1430 multivariate generalized linear mixed model to examine factors associated with perinatal mortality, including study site as a random effect. Of 1,745 1 1 pregnant women included in the cohort study, 1,679 women gave birth Stephanie Richard, Benjamin J. Seidman1, Mustafa Mahfuz4, (4 maternal deaths, 12 abortions, and 50 unknown pregnancy outcomes). Rogawski5, Eric Houpt5, Gagandeep Kang6, Estomih children were alive at 7 days of life. Perinatal mortality in babies born to women without danger Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh, 5University signs was 3. Maternal factors were also important Thohoyandou, South Africa factors in modifying the effect of some of these factors. Interventions should therefore not only target these factors but also consider the Poor growth in early childhood is considered to have both shortand longrelationships that exist between them. Trends in vector densities, sporozoite rates, but illness symptoms did not have an effect on size at fve years. Phenotypic enrolment and socioeconomic status were both positively related to all resistance profle of the malaria vectors as well as target-site resistance of the growth outcomes. Longitudinal markers of environmental enteric and metabolic resistance patterns were also monitored. Biting rates have reduced from an average of 35 bites per person per night in 2009 to 1431 an average of 8 bites per person per night in 2017. Long3 of vector control interventions rely on the knowledge of the local vectors 1University of Queensland, Brisbane, Australia, 2International Centre for for effective programs. Changes in vector behaviors and transmission Diarrhoeal Disease Research, Bangladesh, Dhaka, Bangladesh, 3Swiss intensities are essential in directing vector control interventions and Tropical and Public Health Institute, Basel, Switzerland measuring the impacts of such interventions. Growth impairment in children continues to be a leading global health concern, despite improvement in recent decades. An understanding of 1433 factors associated with growth could contribute to public health efforts. Barde7, Yahaya Signifcant factors were included in a stepwise regression to identify the M. Okeke1, Aklilu Seyoum9, Dereje Dengela10, fnal combination of factors infuencing the outcome. Children in our Uwem Inyang11, Jessica Kafuko11, Bradford Lucas9, Pamela Dasher9, sample were on average 1. Entomological monitoring was conducted from June to University, Bauchi, Nigeria, 8Department of Biological Sciences, Usmanu December in 3 districts (2 sprayed: Koulikoro & Baroueli and 1 adjacent Danfodiyo University, Sokoto, Nigeria, 9U. Associates, Bamako, Mali, 2Programme National de Lutte Contre le However, temporal data suggest a transition to increased outdoor biting Paludisme, Bamako, Mali, 3U. We fnd an association between places United Kingdom with more outdoor biting and a reduced effcacy of indoor vector control. Although previous tests demonstrated effectiveness of insecticide-based interventions. Russell1, Min Myo2, Abraham Mnzava3, exposure time (5s, 30s, 1min up to 2 min) in the tube assays in laboratory. Effe Espino4, Robert Farlow5 the mortality data were calibrated against overnight release recapture data 1Australian Institute of Tropical Health and Medicine, Cairns, Australia, from enclosure around experimental huts incorporating treated inserts. In the experimental have been successful, being responsible for >80% of the reductions huts with enclosure, mortality of An. In this environment of limited treated inserts was 55% compared to similar rate (44%) of mosquitoes recommended interventions choices, vector surveillance has had a limited that contacted the inserts treated with fuorescent dusts. However, the threat posed by that all host-seeking female mosquitoes that contacted beta-cyfuthrin increasing insecticide resistance and residual transmission has led to treated inserts during host-seeking were killed. Beta-cyfuthrin showed an anticipated rollout of new interventions incorporating new/multiple great promise for providing prolonged control of pyrethroid resistant An. How vector data is being collected and used today and the limitations of Insecticide-based interventions are reducing malaria burden. Unfortunately, the data argue for an invigoration and investment in the public health growing insecticide resistance in malaria vectors is threatening these entomologist discipline. However, the extent of the impact of this resistance notably, elevate the role of the public health entomologist in the decision-making metabolic resistance on the effectiveness of insecticide-based interventions process, especially in countries seeking to eliminate malaria. Thus, different parasites might contribute to Biology and Vaccines Unit, Institut Pasteur Paris, Paris, France, 4Unite the variable disease presentations observed in adult patients with severe Biologie des Interactions Hote-Parasite, Institut Pasteur Paris, Paris, France malaria. This fnding has important implications in the future development of malaria adjunctive therapies. Ballo1, by which the parasite is able to enter the Duffy negative reticulocytes Cheick Oumar P. Sangare1, Boubou Sangare1, Demba Dembele1, are unknown but two possible mechanisms have been suggested in Aboubecrin Haidara1, Aliou Traore1, Ogobara K. Malaria transmission to the mosquito relies on gametocytes location of polymorphic residues for these two genes by 3-D modeling. Interestingly we observed no signifcant difference for the gametocyte infectivity in the feld. The number of oocyst positive mosquito and oocyst load per mosquito Rathod2, Joseph D. Dissecting factors infuencing gametocytes areas with lower malaria transmission intensity, such as India, the risk of infectivity will highlight biomarkers associated with malaria transmission renal failure, severe jaundice, pulmonary edema, and multi-organ failure and provide potential targets for transmission blocking strategies and new increases with age. Despite the different disease spectrum and higher tools for malaria transmission screening. Analysis of the root causes of the outbreak, fndings from outbreak Homologous boosting of antibody in convalescence was common. Among response activities, and lessons learned in integrating civilian and military children with non-O blood groups, cluster analysis of antibody profles efforts will be presented. By contrast, in children with blood group O, 1447 only convalescent plasma from severe malaria showed higher recognition of tested isolates.
Treatment of constpaton involves administering oral laxatves in the frst instance medicine disposal buy lumigan 3 ml lowest price, along with advice on a nutritous diet high in fbre and fuid intake if appropriate medications 512 cheap 3 ml lumigan amex, regular exercise and lifestyle modifcatons to symptoms glaucoma order lumigan cheap prevent a recurrence treatment non hodgkins lymphoma 3 ml lumigan mastercard. Prolonged constpaton can lead to a variety of complicatons including haemorrhoids, impacton, hypertension and bowel perforaton in extreme cases (Smeltzer et al. This increased frequency is usually accompanied by increased volume, increased urgency and increased liquidity of the stool. Some individuals may also experience pain that may be abdominal and/or rectal in nature. For example, diarrhoea caused by infectve agents (as in the case of food poisoning) is acute and usually self-limitng, whereas diarrhoea secondary to an underlying conditon such as ulceratve colits may be more chronic in nature. Complicatons of diarrhoea can include fuid and electrolyte imbalance, which can in extreme cases lead to cardiac arrhythmias and other cardiac complicatons. If diarrhoea is extreme or prolonged, intravenous fuid replacement may be required. Priorites of nursing management focus on maintaining the patent’s dignity, facilitatng good personal hygiene, ensuring and encouraging adequate fuid replacement and ofering reassurance and support as necessary. Where possible, it is prudent to identfy the underlying cause of the diarrhoea by sending a stool sample to the laboratory for analysis, among other diagnostc tests. Treatments for diarrhoea may include fuid replacement and electrolyte replacement, antdiarrhoeal agents such as loperamide or codeine preparatons to reduce intestnal motlity, and antmicrobial agents if an infectve organism has been identfed (Young Johnson 2008). Nausea and vomiting Nausea is the feeling or sensaton of sickness and the desire to vomit, which may or may not result. Vomitng is forceful expulsion of the gastric contents, which is usually preceded by nausea. It is important to note that vomitng can be a signifcant presentng feature of a number of conditons and can provide a useful indicaton of potental underlying conditons or the end diagnosis. Other symptoms that ofen accompany nausea and vomitng include sweatng, increased salivaton and tachycardia. If nausea and/or vomitng are prolonged or severe, a number of potental outcomes can result, such as dehydraton, electrolyte imbalance, weight loss, acid erosion of the teeth and oesophageal tears leading to haematemesis (vomitng blood), although these are usually superfcial and heal quickly. Nursing care of conditions related to the digestive system Chapter 14 Priorites of nursing care are directed towards identfying the underlying cause so that specifc treatment can be initated, in additon to correctng fuid and electrolyte imbalance and reassuring and supportng the patent. Antemetc medicatons such as ondansetron or metoclopramide may be prescribed in an atempt to alleviate nausea and vomitng. Cancers of the digestive system Cancer can afect any part of the digestve system, with varying disease manifestatons, progression and consequences. Diagnosis the number and nature of investgatons undertaken to reach a diagnosis will be determined by the patent’s presentng features and the locaton of the presentng complaint. The signs and symptoms of cancers of the digestve tract will vary depending on the part or area afected. Commonly presentng signs and symptoms include weight loss, loss of appette, an altered eatng patern, tredness, nausea and vomitng, and anaemia. More specifc signs and symptoms related to the specifc part or area afected may include dysphagia, dyspnoea, dyspepsia, a feeling of fullness, haematemesis, abdominal pain and/or distension, an altered bowel patern, altered stools including malaena, rectal bleeding, tenesmus (the feeling of a need to pass stool even when the rectum is empty) and a palpable mass in the afected region. In additon to reaching a diagnosis of cancer, it is also normal practce to ascertain the extent of the cancer. Stages of cancer progression generally range from stage 1, in which the tumour is confned to its primary site, through to stage 5, which involves extensive spread of the cancer to tssues and organs in other parts of the body. The earlier the stage of the cancer at the tme of diagnosis, the beter the prognosis for the patent. Treatment Treatment of cancer will be determined by a number of factors including the site, type and stage of the cancer, the impact it has had on the patent, the antcipated efcacy of interventons, their efects on the patent and any comorbidity. Standard cancer treatments that are usually employed include surgery, where appropriate, chemotherapy, radiotherapy, photodynamic therapy or indeed any combinaton of these. A holistc and multdisciplinary approach to patent care is essental when caring for a patent with a diagnosis of cancer of the digestve system who is undergoing treatment. The plan of nursing care depends on the individual patent’s specifc diagnosis, the partcular treatment regimen prescribed and the patent’s response to that treatment. Priorites of nursing care focus on: • psychological care; • reassurance and promoton of the patent’s dignity; • observing and documentng the vital signs and the patent’s conditon; • preventng infectons; • maintaining a high level of personal hygiene; • managing symptoms such as pain, nausea, vomitng, diarrhoea, poor appette and dehydraton; • maintaining skin integrity; • encouraging sleep and rest. It is essental to involve members of the multdisciplinary team such as the diettan, stoma care specialist, chaplain, social worker, counsellor and, where necessary, palliatve care team. It is also Part 2 Adult Medical and Surgical Nursing Oesophagus Lesser curvature Fundus Greater curvature Pyloric sphincter Common sites for peptic ulcer Figure 14. Peptic ulcer disease Peptc ulcer disease can afect the oesophagus, stomach and duodenum. The lining of afected area is damaged, usually by increased acid secreton, leading to infammaton and ulceraton (Figure 14. Peptc ulcer disease can range from mild, causing few symptoms, to severe and even life-threatening, as in the case of perforaton of the gastrointestnal wall. Duodenal ulcers occur more commonly than gastric ulcers, with gastric ulcers occurring most commonly on the lesser curvature of the stomach (Nair, 2009a). Peptc ulcer disease can afect individuals of any age but occurs most commonly in the 40–60-year age group (Smeltzer et al. The presence of a partcular Gram-negatve bacterium, Helicobactor pylori, in the stomach accounts for 70–80% of gastric ulcers (Ford et al. Other factors that are thought to lead to peptc ulcer disease include smoking, alcohol, stress, excessive cafeine intake, prolonged use of aspirin, nonsteroidal ant-infammatory drugs or cortcosteroids, and genetc predispositon (Mynat et al. Clinical features and complications Symptoms may vary from mild to severe, depending on the locaton and degree of ulceraton, and can occur intermitently. Common symptoms include: • epigastric pain that occurs when the stomach is empty and is usually relieved by intake of food, milk or antacids; • dyspepsia; • loss of appette; • heartburn due to refux of gastric acid, and belching; • nausea and vomitng; • malaena. Around 20–30% of patents present in the frst instance with haemorrhage or perforaton in the absence of any preceding symptoms (Smeltzer et al. Perforaton is erosion of the ulcer through the gastric or duodenal Nursing care of conditions related to the digestive system Chapter 14 wall into the peritoneal cavity, leading to chemical and bacterial peritonits (Smeltzer et al. These complicatons are potentally life-threatening and require emergency treatment. Another complicaton of peptc ulcer disease is pyloric stenosis, in which the pyloric sphincter becomes obstructed due to scarring or stenosis, inhibitng the fow of stomach contents into the duodenum. In the case of ulcers secondary to Helicobactor pylori infecton, antbiotc therapy using two or three antbiotcs (amoxicillin, clarithromycin and metronidazole, for example) along with a proton pump inhibitor such as omeprazole will be prescribed for 10–14 days in an atempt to eradicate the bacteria; this efects a permanent cure in 90% of cases (Norton et al. Proton pump inhibitors and H2 receptor antagonists such as ranitdine are used in the treatment of ulcers that are not associated with Helicobactor pylori. Antacids such as calcium carbonate or magnesium salts can be used to treat symptoms such as heartburn and dyspepsia but ofen provide only temporary relief. Long-term maintenance therapy with medicaton may be required to prevent recurrence (Smeltzer et al. The management of peptc ulcer disease should also incorporate advice and guidance on relevant lifestyle changes. Nursing management Nausea and vomitng can be treated with an antemetc such as prochlorperazine (Stemetl) or metoclopramide. The patent’s response to the medicaton administered, and the efects and side efects, must be observed, documented and reported to the medical team when necessary. Complicatons associated with peptc ulcer disease include haemorrhage, perforaton and pyloric stenosis. If any of these complicatons occur, intravenous access will need to be established and fuid replacement initated to correct hypovolaemia. In additon, the inserton of a nasogastric tube will allow aspiraton to decompress and empty the stomach, and there should be contnual monitoring of vital signs and ongoing reassurance and support. Oxygen therapy and monitoring of oxygen saturaton levels will be required if there is haemorrhage, and replacement of blood components may become necessary if the haemorrhage is severe. Intravenous antbiotc therapy may be required to prevent septc shock where a perforaton has occurred. Depending on the type and severity of the complicaton, the patent may also need to be prepared for endoscopy, as in the case of pyloric stenosis (to dilate the pylorus), or surgery, as in the case of perforaton. In order to reduce the risk of recurrence of peptc ulcer disease, the patent should be advised to stop smoking, reduce their cafeine and alcohol intake and modify their diet to include small regular meals and avoid foods that trigger gastrointestnal symptoms. Medicatons such as aspirin and nonsteroidal ant-infammatory drugs should be avoided where possible.
The Company medicine just for cough order lumigan 3ml without prescription, if required by the rules and regulations of the Commission medicine 95a generic 3ml lumigan, shall file the Preliminary Prospectus or the Prospectus with the Commission pursuant to medicine 02 safe 3 ml lumigan Rule 424(b) medications 44334 white oblong cheap lumigan 3ml on-line. The Company has not issued any share capital since its most recently filed Form 6-K. No Person has any right of first refusal, preemptive right, right of participation, or any similar right to participate in the transactions contemplated by the Transaction Documents. There are no outstanding securities or instruments of the Company or any Subsidiary that contain any redemption or similar provisions, and there are no contracts, commitments, understandings or arrangements by which the Company or any Subsidiary is or may become bound to redeem a security of the Company or such Subsidiary. The Company does not have any share appreciation rights or “phantom share” plans or agreements or any similar plan or agreement. All of the outstanding share capital of the Company are duly authorized, validly issued, fully paid and nonassessable, have been issued in compliance with all federal and state securities laws where applicable, and none of such outstanding shares was issued in violation of any preemptive rights or similar rights to subscribe for or purchase securities. Except for the Required Approvals, no further approval or authorization of any shareholder, the Board of Directors or others is required for the issuance and sale of the Securities. There are no shareholders agreements, voting agreements or other similar agreements with respect to the Company’s share capital to which the Company is a party or, to the knowledge of the Company, between or among any of the Company’s shareholders. The Company has never been an issuer subject to Rule 144(i) under the Securities Act. The Company does not have pending before the Commission any request for confidential treatment of information. Except for the issuance of the Securities contemplated by this Agreement or as set forth on Schedule 3. There has not been, and to the knowledge of the Company, there is not pending or contemplated, any investigation by the Commission involving the Company or any current or former director or officer of the Company. The Commission has not issued any stop order or other order suspending the effectiveness of any registration statement filed by the Company or any Subsidiary under the Exchange Act or the Securities Act. No labor dispute exists or, to the knowledge of the Company, is imminent with respect to any of the employees of the Company, which could reasonably be expected to result in a Material Adverse Effect. None of the Company’s or its Subsidiaries’ employees is a member of a union that relates to such employee’s relationship with the Company or such Subsidiary, and neither the Company nor any of its Subsidiaries is a party to a collective bargaining agreement, and the Company and its Subsidiaries believe that their relationships with their employees are good. To the knowledge of the Company, no executive officer of the Company or any Subsidiary, is, or is now expected to be, in violation of any material term of any employment contract, confidentiality, disclosure or proprietary information agreement or non-competition agreement, or any other contract or agreement or any restrictive covenant in favor of any third party, and the continued employment of each such executive officer does not subject the Company or any of its Subsidiaries to any liability with respect to any of the foregoing matters. Neither the Company nor any Subsidiary: (i) is in default under or in violation of (and no event has occurred that has not been waived that, with notice or lapse of time or both, would result in a default by the Company or any Subsidiary under), nor has the Company or any Subsidiary received notice of a claim that it is in default under or that it is in violation of, any indenture, loan or credit agreement or any other agreement or instrument to which it is a party or by which it or any of its properties is bound (whether or not such default or violation has been waived), (ii) is in violation of any judgment, decree or order of any court, arbitrator or other governmental authority or (iii) is or has been in violation of any statute, rule, ordinance or regulation of any governmental authority, including without limitation all foreign, federal, state and local laws relating to taxes, environmental protection, occupational health and safety, product quality and safety and employment and labor matters, except in each case of (i), (ii) and (iii) as could not have or reasonably be expected to result in a Material Adverse Effect. Any real property and facilities held under lease by the Company and the Subsidiaries are held by them under valid, subsisting and enforceable leases with which the Company and the Subsidiaries are in compliance in all material respects. None of, and neither the Company nor any Subsidiary has received a notice (written or otherwise) that any of, the Intellectual Property Rights has expired, terminated or been abandoned, or is expected to expire or terminate or be abandoned, within two (2) years from the date of this Agreement except as would not reasonably be expected to have a Material Adverse Effect. To the knowledge of the Company, all such Intellectual Property Rights are enforceable and there is no existing infringement by another Person of any of the Intellectual Property Rights. The Company and its Subsidiaries have taken reasonable security measures to protect the secrecy, confidentiality and value of all of their intellectual properties, except where failure to do so could not, individually or in the aggregate, reasonably be expected to have a Material Adverse Effect. The Company and the Subsidiaries are insured by insurers of recognized financial responsibility against such losses and risks and in such amounts as are prudent and customary in the businesses in which the Company and the Subsidiaries are engaged, including, but not limited to, directors and officers insurance coverage. Neither the Company nor any Subsidiary has any reason to believe that it will not be able to renew its existing insurance coverage as and when such coverage expires or to obtain similar coverage from similar insurers as may be necessary to continue its business without a significant increase in cost. The Company and the Subsidiaries are in material compliance with any and all applicable requirements of the Sarbanes-Oxley Act of 2002 that are effective as of the date hereof, and any and all applicable rules and regulations promulgated by the Commission thereunder that are effective as of the date hereof and as of the Closing Date. The Company and the Subsidiaries have established disclosure controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)) for the Company and the Subsidiaries and designed such disclosure controls and procedures to ensure that information required to be disclosed by the Company in the reports it files or submits under the Exchange Act is recorded, processed, summarized and reported, within the time periods specified in the Commission’s rules and forms. The Company’s certifying officers have evaluated the effectiveness of the disclosure controls and procedures of the Company and the Subsidiaries as of the end of the period covered by the most recently filed Form 20-F under the Exchange Act (such date, the “Evaluation Date”). The Company presented in its most recently filed Form 20-F under the Exchange Act the conclusions of the certifying officers about the effectiveness of the disclosure controls and procedures based on their evaluations as of the Evaluation Date. Since the Evaluation Date, there have been no changes in the internal control over financial reporting (as such term is defined in the Exchange Act) that have materially affected, or is reasonably likely to materially affect, the internal control over financial reporting of the Company and its Subsidiaries. Except as set forth in the Preliminary Prospectus and the Prospectus, no brokerage or finder’s fees or commissions are or will be payable by the Company or any Subsidiary to any broker, financial advisor or consultant, finder, placement agent, investment banker, bank or other Person with respect to the transactions contemplated by the Transaction Documents. Other than for Persons engaged by any Purchaser, if any, the Purchasers shall have no obligation with respect to any fees or with respect to any claims made by or on behalf of other Persons for fees of a type contemplated in this Section that may be due in connection with the transactions contemplated by the Transaction Documents. The Company is not, and is not an Affiliate of, and immediately after receipt of payment for the Securities, will not be or be an Affiliate of, an “investment company” within the meaning of the Investment Company Act of 1940, as amended. The Company shall conduct its business in a manner so that it will not become an “investment company” subject to registration under the Investment Company Act of 1940, as amended. Except with respect to the material terms and conditions of the transactions contemplated by the Transaction Documents, the Company confirms that neither it nor any other Person acting on its behalf has provided any of the Purchasers or their agents or counsel with any information that it believes constitutes or might constitute material, non-public information which is not otherwise disclosed in the Prospectus. The Company understands and confirms that the Purchasers will rely on the foregoing representation in effecting transactions in securities of the Company. All of the disclosure furnished by or on behalf of the Company to the Purchasers regarding the Company and its Subsidiaries, their respective businesses and the transactions contemplated hereby, including the Disclosure Schedules to this Agreement, is true and correct in all material respects and does not contain any untrue statement of a material fact or omit to state any material fact necessary in order to make the statements made therein, in the light of the circumstances under which they were made, not misleading. The press releases disseminated by the Company during the twelve months preceding the date of this Agreement taken as a whole do not contain any untrue statement of a material fact or omit to state a material fact required to be stated therein or necessary in order to make the statements therein, in the light of the circumstances under which they were made and when made, not misleading. The Company acknowledges and agrees that no Purchaser makes or has made any representations or warranties with respect to the transactions contemplated hereby other than those specifically set forth in Section 3. Assuming the accuracy of the Purchasers’ representations and warranties set forth in Section 3. Based on the consolidated financial condition of the Company as of the Closing Date, after giving effect to the receipt by the Company of the proceeds from the sale of the Securities hereunder, (i) the fair saleable value of the Company’s assets exceeds the amount that will be required to be paid on or in respect of the Company’s existing debts and other liabilities (including known contingent liabilities) as they mature, (ii) the Company’s assets do not constitute unreasonably small capital to carry on its business as now conducted and as proposed to be conducted including its capital needs taking into account the particular capital requirements of the business conducted by the Company, consolidated and projected capital requirements and capital availability thereof, and (iii) the current cash flow of the Company, together with the proceeds the Company would receive, were it to liquidate all of its assets, after taking into account all anticipated uses of the cash, would be sufficient to pay all amounts on or in respect of its liabilities when such amounts are required to be paid. The Company does not intend to incur debts beyond its ability to pay such debts as they mature (taking into account the timing and amounts of cash to be payable on or in respect of its debt). The Company has no knowledge of any facts or circumstances which lead it to believe that it will file for reorganization or liquidation under the bankruptcy or reorganization laws of any jurisdiction within one year from the Closing Date. Neither the Company nor any Subsidiary is in default with respect to any Indebtedness. Except for matters that would not, individually or in the aggregate, have or reasonably be expected to result in a Material Adverse Effect, the Company and its Subsidiaries each (i) has made or filed all United States federal, state and local income and all foreign income and franchise tax returns, reports and declarations required by any jurisdiction to which it is subject, (ii) has paid all taxes and other governmental assessments and charges that are material in amount, shown or determined to be due on such returns, reports and declarations and (iii) has set aside on its books provision reasonably adequate for the payment of all material taxes for periods subsequent to the periods to which such returns, reports or declarations apply. There are no unpaid taxes in any material amount claimed to be due by the taxing authority of any jurisdiction, and the officers of the Company or of any Subsidiary know of no basis for any such claim. The Company’s independent registered public accounting firm is as set forth in the Prospectus. To the knowledge and belief of the Company, such accounting firm (i) is a registered public accounting firm as required by the Exchange Act and (ii) shall express its opinion with respect to the financial statements to be included in the Company’s Annual Report for the fiscal year ended December 31, 2019. The Company acknowledges and agrees that each of the Purchasers is acting solely in the capacity of an arm’s length purchaser with respect to the Transaction Documents and the transactions contemplated thereby. The Company further acknowledges that no Purchaser is acting as a financial advisor or fiduciary of the Company (or in any similar capacity) with respect to the Transaction Documents and the transactions contemplated thereby and any advice given by any Purchaser or any of their respective representatives or agents in connection with the Transaction Documents and the transactions contemplated thereby is merely incidental to the Purchasers’ purchase of the Securities. The Company further represents to each Purchaser that the Company’s decision to enter into this Agreement and the other Transaction Documents has been based solely on the independent evaluation of the transactions contemplated hereby by the Company and its representatives. Anything in this Agreement or elsewhere herein to the contrary notwithstanding (except for Sections 3. The Company acknowledges that such aforementioned hedging activities do not constitute a breach of any of the Transaction Documents. The operations of the Company and its Subsidiaries are and have been conducted at all times in compliance with applicable financial record-keeping and reporting requirements of the Currency and Foreign Transactions Reporting Act of 1970, as amended, applicable money laundering statutes and applicable rules and regulations thereunder (collectively, the “Money Laundering Laws”), and no action, suit or proceeding by or before any court or governmental agency, authority or body or any arbitrator involving the Company or any Subsidiary with respect to the Money Laundering Laws is pending or, to the knowledge of the Company or any Subsidiary, threatened. Each Purchaser, for itself and for no other Purchaser, hereby represents and warrants as of the date hereof and as of the Closing Date to the Company as follows (unless as of a specific date therein, in which case they shall be accurate as of such date): (a) Organization; Authority. Such Purchaser is either an individual or an entity duly incorporated or formed, validly existing and in good standing under the laws of the jurisdiction of its incorporation or formation with full right, corporate, partnership limited liability company or similar power and authority to enter into and to consummate the transactions contemplated by this Agreement and otherwise to carry out its obligations hereunder and thereunder. The execution and delivery of this Agreement and performance by such Purchaser of the transactions contemplated by this Agreement have been duly authorized by all necessary corporate, partnership, limited liability company or similar action, as applicable, on the part of such Purchaser. Each Transaction Document to which it is a party has been duly executed by such Purchaser, and when delivered by such Purchaser in accordance with the terms hereof, will constitute the valid and legally binding obligation of such Purchaser, enforceable against it in accordance with its terms, except: (i) as limited by general equitable principles and applicable bankruptcy, insolvency, reorganization, moratorium and other laws of general application affecting enforcement of creditors’ rights generally, (ii) as limited by laws relating to the availability of specific performance, injunctive relief or other equitable remedies and (iii) insofar as indemnification and contribution provisions may be limited by applicable law. Such Purchaser is acquiring the Securities as principal for its own account and has no direct or indirect arrangement or understandings with any other persons to distribute or regarding the distribution of such Securities (this representation and warranty not limiting such Purchaser’s right to sell the Securities pursuant to the Registration Statement or otherwise in compliance with applicable federal and state securities laws). Such Purchaser is acquiring the Securities hereunder in the ordinary course of its business.
Before the current control program was undertaken acute treatment discount lumigan 3ml free shipping, it was estimated that more than 10 million people were infected medicine 802 buy cheap lumigan on-line. In Japan treatment centers for depression generic 3ml lumigan amex, the human infection is largely under control and only a few hundred carriers remain treatment endometriosis purchase on line lumigan. In the Americas, Brazil alone has an estimated 8 to 12 million infected individuals. In that country, tests carried out during preparations for its schistosomiasis control program revealed a positivity rate of 22. In some localities in northeastern Minas Gerais, Brazil, 100% of the population was found to be infected. The infection has spread in some areas because of new irrigation projects and the migration of infected populations. In Brazil, schistosomiasis has spread to the states of Goias, Maranhao, Para, Parana, Santa Catarina, Sao Paulo (where there are several isolated foci), and from the northeast to southern Minas Gerais (Katz and Carvalho, 1983). Despite the fact that several countries have managed to reduce the occurrence of schistosomiasis through vigorous control programs, its prevalence has changed little in recent decades because of the expansion of irrigation and the human migrations mentioned earlier. Reports published in 1999, based on research in selected communities from different countries, gave the following prevalence ranges for S. In addition, there are an estimated half million infected persons in Madagascar. In 1998, two surveys carried out in different municipalities of Sao Paulo State in Brazil showed 0. The Disease in Man: Approximately 90% of schistosome infections in humans are asymptomatic. However, some patients suffer acute respiratory abnormalities with radiographic signs and unspecific symptoms similar to those of influenza. There can be more significant morbidity, and even mortality, from fibrotic reactions to parasite eggs laid in host tissue, leading especially to portal hypertension in the case of S. However, the disease’s clinical presentation has changed over the last 10 to 15 years thanks to specific chemotherapy for schistosomiasis and to environmental changes in many countries, and its earlier hepatosplenic and other manifestations (ascites, gastric hemorrhage, splenomegaly, cor pulmonale, glomerulopathy) are now less severe (Andrade, 1998). Between 6% and 27% of infected women suffer from genital lesions, but the nature and treatment of these lesions is not yet understood (Feldmeier, 1998). Occasionally, the eggs reach the central nervous system and produce a granulomatous reaction. When there are only a few eggs and they are widely scattered, no signs are observed, but large granulomas can cause increased intracranial pressure and focalized signs, often in the lumbosacral spinal cord (Ferrari, 1999; Pittella, 1997). The seriousness of the disease is dictated by the parasite burden and the length of time the patient has been infected; both factors affect the number of eggs that settle in host tissues, which is the main determinant of chronic pathology. School-age children and occupational groups that spend time frequently and for long periods in water, such as fishermen and rice growers, have more intense infections because of the accumulation of parasites from repeated infections. However, there is a limit to this accumulation because the schistosomes generate concomitant immunity; in other words, the adult forms of the parasite partially protect against new infections by schistosomula. The symptomatology of schistosomiasis may be divided into four phases, according to the evolution of the parasitosis. It is commonly manifested by a cutaneous allergy to the parasite’s products, which occurs with greater frequency and intensity in reinfections. At first there are petechiae with edema and pruritus; these are followed by urticaria, which can become vesicular and last from 36 hours to 10 days. The second phase occurs when the schistosomula invade the pulmonary capillaries. In most cases there are no clinical manifestations, although massive infections can produce pneumonitis with coughing and asthma-like crises, along with eosinophilic infiltration. The third phase develops when the parasite matures inside the liver and oviposition begins to take place in the corresponding venules. It is believed that these symptoms represent an acute immune response to antigens released by the eggs, with the formation of abundant cytokines. The fourth, or chronic or granulomatous phase, reflects the tissue response to the deposition of eggs. The antigens of the eggs that are retained in the tissues generate a cell-mediated immune response that forms granulomas around the eggs. When the granulomas become abundant in a tissue, they converge and can invade an important part of the organ. Prior stimulation of the patient by antigens of the adult parasite and the intervention of tumor necrosis factor alpha seem to play an important role in the formation of granulomas (Leptak and McKerrow, 1997). Over time, they spread to the liver and produce interlobular fibrosis and portal hypertension, ascites, and splenomegaly. In the chronic phase, the following clinical forms can be distinguished: intestinal, hepatointestinal, hepatosplenic, and pulmonary. Ultrasound revealed hepatomegaly in 35% of the infected individuals and splenomegaly in 80%, both of which were associated with a high parasite burden and were less notable in those who had already been treated with praziquantel. Mild periportal fibrosis was common, and signs of portal hypertension were observed in 2% of the subjects. The signs of chronic disease are usually persistent diarrhea and abdominal pain with hepatomegaly or splenomegaly. Papillomatous folds, pseudoabscesses, and miliary pseudotubercles develop in the wall of the bladder, and sometimes there is total fibrosis of the organ. The main symptoms are painful and frequent urination, terminal hematuria, suprapubic pain, and recurrent urinary infections. The eggs may also travel to the intestine, especially the venules that drain the rectum, and they may be eliminated in the feces. Evidence suggests that vesical schistosomiasis may be a predisposing condition for malignant tumors because of the continuous irritation produced by the eggs. Both infection and morbidity rates were higher in children aged 7 to 14 years old. Treatment with praziquantel resolved more than 80% of the urinary tract lesions within a year (Traore, 1998). Hepatomegaly occurs in approximately 50% of the cases, but portal hypertension is not seen. There is also an acute form of schistosomiasis, often referred to as Katayama fever, which develops four to six weeks after a massive primary infection with S. The clinical manifestations are similar in some respects to those of serum disease: fever, eosinophilia, lymphadenopathy, hepatosplenomegaly, and sometimes dysentery. Because of the clinical manifestations and the fact that the disease occurs at the beginning of oviposition, it is believed that this syndrome is caused by the formation of antigen-antibody complexes in the bloodstream. Prevalence rates in cattle have been found to be as high as 62% (Bangladesh), 90% (Sudan), and 92% (Zimbabwe). As in man, schistosomiasis in cattle has an acute phase, caused when recently matured parasites release large quantities of eggs in the intestinal mucosa, and a chronic phase, during which the damage is caused by the reaction to antigens produced by eggs trapped inside tissues. The former, referred to as the intestinal syndrome, occurs seven to nine weeks after a massive initial infection and causes severe hemorrhagic lesions in the intestinal mucosa, with infiltration of eosinophils, lymphocytes, macrophages, and plasmocytes, along with profuse diarrhea or dysentery, dehydration, anorexia, anemia, hypoalbuminemia, weight loss, and retarded development. The duration of the disease varies depending on the parasite burden, and recovery is spontaneous. The chronic phase, or hepatic syndrome, is a cell-mediated immune response to antigens from the trapped eggs. As in man, the reaction leads to the formation of inflammatory foci, granulomas, fibroses, and ultimately, the obstruction of portal irrigation. The chronic disease occurs in animals that have been repeatedly exposed to infections with large numbers of cercariae, and the principal manifestations are emaciation, anemia, eosinophilia, and hypoalbuminemia (Soulsby, 1982). Unlike man, animals do not appear to be susceptible to splenomegaly or esophageal varices, but the presence of dead parasites can cause them to develop enlarged follicles or lymph nodes, as well as venous thromboses, with infarct of the organ. In addition to the liver, the schistosome eggs can settle in the intestinal wall, lungs, kidneys, bladder, and other organs, where they cause damage and symptoms in proportion to the parasite burden. Cattle have also been reported to have obstructive phlebitis caused by the presence of adult parasites in the veins. While some areas are making progress through vigorous control campaigns, the infection is spreading to others in the wake of new irrigation projects or carried by individuals. Moreover, the geographic range of the intermediate hosts is greater than that of the human infection.
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