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Chapter: 1 Introduction
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Suggested Citation:"1 Introduction." National Academies of Sciences, Engineering, and Medicine. 2017. Integrating Clinical Research into Epidemic Response: The Ebola Experience. Washington, DC: The National Academies Press. doi: 10.17226/24739.
Ebola has been known since 1976 when two outbreaks occurred, one in the Democratic Republic of the Congo, then known as Zaire, and the other in what is now South Sudan (Johnson et al., 1977). Ebola is a serious illness, transmitted from person to person by direct contact with infected body fluids, with a high mortality rate even with good clinical care (see Box 1-1). Until 2014, however, previous outbreaks had been limited in size and duration, occurring in relatively isolated communities in Central Africa and Uganda, with at most a few hundred cases and deaths in each outbreak but no cross-border or international spread (CDC, 2016c). Much was learned about the virus from previous outbreaks, but there was little knowledge of case management or the clinical sequelae among survivors because these outbreaks affected a limited number of individuals and were contained in isolated settings. The opportunity to make clinical observations was therefore restricted. Research on drugs and vaccines for Ebola was accordingly also limited in support and scope; the research was primarily focused on early preclinical development and was not a particularly high priority for the major international medical research organizations, including military health research institutes in the United States and elsewhere, or for the pharmaceutical industry (Burki, 2011). There was, nonetheless, some steady progress, including nonhuman primate challenge studies on investigational therapeutic agents and vaccines and also some very limited human Phase 1 studies of vaccine candidates at the beginning of 2014 (Gebre et al., 2014). Because of the nature of the disease, there was no way to create an experimental human infection model to test the efficacy of these products. Testing these products would require that a natural outbreak of
BOX 1-1
Ebola Virus Disease
Ebola virus disease is a serious, acute illness characterized by fever, vomiting, diarrhea, impaired kidney and liver functions, and internal and external bleeding. Ebola is introduced to humans through contact with the blood, bodily fluids, or organs of infected animals, such as chimpanzees, gorillas, fruit bats, antelope, and a variety of bush mammals that are often consumed as food. It then spreads person to person through direct contact with the bodily fluids (e.g., blood, secretions) of infected persons, including those who are already deceased and harbor a high viral load. The time between infection and onset of symptoms ranges from 2 to 21 days. The initial symptoms of Ebola—fever, fatigue, muscle pain, sore throat, and headache—are similar to the symptoms of many common infections such as malaria, typhoid fever, and meningitis. Mortality from Ebola is variable, ranging from 25 to 90 percent, depending on the strain of the virus, the condition of the host (e.g., age; children of age <6 years are at higher risk of death), and the availability of expert supportive care, including fluid and electrolyte management. Those who survive the disease may continue to harbor the virus in immunologically protected sites such as the central nervous system, eyes, and testes and can still transmit it.
SOURCES: CDC, 2015b; WHO, 2016a.
sufficient size and duration occurred and that researchers could quickly mobilize products, protocols, and participants and implement clinical trials before the outbreak came under control and transmission was halted. And no one knew when, where, or whether this situation would present itself—until the epidemic of 2014–2015.
Conducting clinical research can often seem secondary to addressing the immediate health needs of patients, if not a distraction and unnecessary impediment to public health control activities and patient care in the midst of a public health emergency. However, research is an essential component to epidemic response, as it is the only way to learn how to improve care for current and future patients and to potentially prevent an epidemic from occurring again (Lurie et al., 2013). This is especially true for a disease like Ebola because there were no proven safe and effective therapeutic products or vaccines when the epidemic began. An epidemic, despite the often chaotic environment, is an opportunity to test the efficacy of vaccines and therapeutics that are currently in development. If research quickly reveals a safe and effective therapeutic agent or one that is superior to any available at the time, current patients could reap the benefits as soon as the interven-
tion could be approved, made available, and delivered to those in need. The discovery of a safe and effective vaccine could protect people who are at immediate risk of infection as well as prevent future generations from contracting the disease.
There are established principles for conducting scientifically sound, ethical clinical research. For many years these have been reviewed and refined for the international context, in particular when research is sponsored by high-income countries for conduct in low-income countries. For example, the Declaration of Helsinki states that researchers must obtain the "freely given informed consent" of research subjects and that medical research "must conform to generally accepted scientific principles" and "be preceded by careful assessment of the predictable risks and burdens to the individuals and groups involved" (WMA, 2013, p. 2192). During an epidemic some of the standard practices of research may need to be accelerated or modified in order to work in the specific context of the community and disease. For example, informed consent procedures may need to be sped up or abbreviated, or consent by proxy may be deemed appropriate in situations in which patients are not able to give consent. However, as discussed in more detail in Chapter 2, the core ethical and scientific principles of research must undergird efforts even in the midst of an epidemic. Doing so helps to ensure that research can "quickly and definitively determine the safety and efficacy of interventions and thus provide access for the greatest number of patients to the most effective therapies in the shortest possible time" (Lane et al., 2016, p. 2). In addition, adhering to ethical principles such as "respect for volunteers and study communities, the value of informed consent, and the need for collaborative partnership with affected communities" helps to ensure that affected communities are not exploited and that the researchers gain the trust and buy-in of the community (Lane et al., 2016, p. 2).
Every epidemic is different in terms of the communities affected, the transmission and mortality rates, and the availability of potential treatments (KFF, 2014). The 2014–2015 Ebola epidemic was different from all previous Ebola outbreaks—it was unpredictable and fast moving, crossed borders, affected large numbers of people, was highly deadly, and was exacerbated by the lack of local experience, resources, infrastructure, and the limited number of experienced researchers (Heymann and Wertheimer, 2014). However, the issues raised by conducting research in the midst of the epidemic were not unique to Ebola. The same scientific and ethical questions have arisen in various other epidemics, ranging from the HIV/ AIDS epidemic in the early 1980s to the current Zika epidemic (Deloffre, 2016; Wainberg et al., 2014). Much can be learned from prior debates about conducting research during public health emergencies, in resource-poor settings, or among a population of desperately ill patients. Researchers should not consider each epidemic to be sui generis; rather, the response to
each new epidemic should take advantage of the fact that various epidemics have common elements and build upon the knowledge gained from previous experiences.
CHARGE TO THE COMMITTEE AND STUDY SCOPE
In October 2015, the Office of the Assistant Secretary for Preparedness and Response, the National Institute of Allergy and Infectious Diseases, and the U.S. Food and Drug Administration of the U.S. Department of Health and Human Services charged the National Academies of Sciences, Engineering, and Medicine (the National Academies) with developing a consensus report that explores and analyzes scientific and ethical issues related to clinical trial design, conduct, and reporting. The sponsors stipulated that particular emphasis be given to clinical trials for investigational therapeutic and vaccine candidates for Ebola conducted by the international community in settings where there is limited health care and research infrastructure, focusing on research conducted in Guinea, Liberia, and Sierra Leone during the 2014–2015 epidemic. The information and analysis presented in this report is meant to inform guidelines and best practices for clinical trials of therapeutics and vaccines conducted in response to future outbreaks and epidemics in low-resource settings (see Box 1-2 for the full Statement of Task).
Statement of Task
An ad hoc committee of the National Academies of Science, Engineering, and Medicine will review and conduct an analysis of the clinical trials conducted during the 2014–2015 Ebola virus disease outbreak in West Africa. The final deliverable from this committee will be a consensus report that explores and analyzes the scientific and ethical issues related to clinical trial design, conduct, and reporting. Particular emphasis will be given to clinical trials for vaccine and therapeutic candidates for Ebola conducted by the international community in settings where there is limited health care and research infrastructure.
The committee will achieve its objectives by organizing and conducting meetings, interviews, and discussions with key informants in the international research community and in affected countries, including perspectives from government agencies, nongovernmental entities, and others. The final report of the committee will be based on the information gathered at these meetings and key informant interviews and review of the literature and other relevant documentation and communications.
In summary the report will
Assess the scientific value of the different Ebola vaccine and therapeutic clinical trials conducted in Guinea, Liberia, and Sierra Leone and the data derived from them.
Describe the specific context (such as disease pathogenicity, high case fatality, political and health system context, and public opinion) and the ethical and scientific practices and considerations related to the design and conduct of each Ebola clinical trial.
To the extent possible, characterize how these considerations have been addressed in similar contexts previously, drawing on case studies of clinical trials conducted during prior disasters to identify transferable best practices.
Compare pragmatic, ethical, and scientific practices and considerations made in the context of each Ebola clinical trial against existing best practices to identify additional best practices and make recommendations on opportunities for improving future clinical research conducted during public health emergencies.
Make recommendations for how, in the context of an international emerging or reemerging infectious disease event, clinical trials can best be prioritized and conducted to (1) speed data collection; (2) inform clinical management of patients; (3) assess the safety, efficacy, and effectiveness of therapeutics and vaccines; and/or (4) improve/augment outbreak control efforts.
Where possible, identify scientific and ethical principles and practical guidance for clinical trial practices and protocols that balance the rapid need for new, useful information with ethical considerations and scientific rigor amid an emerging and rapidly evolving infectious disease event.
Where possible, identify new ideas for innovative approaches to research in emergency contexts and to alternative methods to evaluate treatments and vaccines.
Such guidance should include options that facilitate a more flexible and accelerated approach.
Address whether adjustments to scientific or ethical standards are appropriate in the conduct of research in outbreak settings and, if so, under what circumstances. If such adjustments are found to be appropriate, specify
How those adjustments should be decided and implemented; and
Current and/or future consequences of any such adjustments to patients themselves or to prevention and treatment strategies.
Identify opportunities for collaborative investment to achieve long-term ethical and scientific gains from clinical trials conducted during emerging infectious disease events.
Develop recommendations for planning activities during the inter-epidemic period to better prepare for and improve the execution of clinical trials during future infectious disease public health emergencies.
To respond to this charge, the National Academies convened a 16-member ad hoc committee composed of experts from a range of disciplines. Members of the committee have expertise in clinical trial conduct and design, biostatistics, infectious disease, public health, health systems, and bioethics as well as considerable experience working in low- and middle-income countries. The committee included members from Africa, Europe, and North America.
STUDY METHODOLOGY
The committee deliberated from February to November 2016, during which time it held three 3-day public workshops in Washington, DC; London; and Monrovia; one 2-hour public webinar; and three 2-day closed meetings. The committee also solicited and considered written statements from stakeholders and members of the public, as well as soliciting information regarding the clinical trials conducted from responsible clinical trial teams. Furthermore, the committee conducted an extensive literature review on relevant topics. (See Appendix A for more information.)
CONTEXT OF THE 2014–2015 EBOLA EPIDEMIC
The 2014–2015 Ebola epidemic, the largest in history, began in December 2013 when a toddler in Guinea became ill, likely as a result of contact with a bat (WHO, 2015d). He died on December 28, 2013, and, soon after, members of his family and several health care workers who treated them also became ill and died. By the end of February 2014, the illness had spread to Conakry, the capital, as well as to other villages and cities. On March 22, the cause was confirmed to be the Zaire species of the Ebola family, and the following day the World Health Organization (WHO) publicly announced the outbreak. The WHO's announcement provided an official count of 49 cases with 29 deaths and noted that reports of suspected cases in Liberia and Sierra Leone, which share a common border with Guinea, were being investigated (WHO, 2014c). Within a few days, Ebola cases were confirmed in both countries (MSF, 2015). By the time the epidemic was nearing its end in early 2016, the epidemic was responsible for 28,616 cases of Ebola, with 11,310 deaths (WHO, 2016a). The WHO declared the emergency phase of the epidemic to be over on March 29, 2016, though flare-ups continued to occur through April (WHO, 2016a).
The three countries at the epicenter of the 2014–2015 epidemic—Guinea, Liberia, and Sierra Leone—were all ill equipped to handle such a serious and quick-moving epidemic. Given its size and rapid spread, the epidemic would have been a challenge for any country to contain. Before the epidemic Liberia and Sierra Leone were in the process of rebuilding
after long civil wars that had spilled over into Guinea, and all three countries suffered from political and social instability, weak health care systems, extreme poverty, and poor infrastructure (International Crisis Group, 2015). In the 2014 United Nations Human Development Index, which ranks 187 countries on the basis of life expectancy, income per capita, and years of schooling, Guinea was ranked 179th, Liberia 175th, and Sierra Leone 183rd (UNDP, 2014). The health systems of each country were weak, with critical shortages of medical doctors and hospital beds (see Table 1-1). Health care facilities were unevenly distributed, inadequately staffed, and lacked the supplies necessary to treat patients and protect health care workers (CIA, 2016; International Crisis Group, 2015). The 2014–2015 Ebola epidemic in the three countries moved quickly, was difficult to contain, and lasted longer than any previous outbreak. In contrast, outbreaks of Ebola in Nigeria, Senegal, and Mali in, respectively, July, August, and October 2014 were contained relatively quickly due to a high state of alert, more robust health systems and public health capacity, and the ability to mobilize and deploy the necessary human and laboratory resources rapidly from within and outside of these countries (WHO, 2015e).
The Ebola epidemic in Guinea, Liberia, and Sierra Leone exposed and strained those countries' already fragile health care and public health systems, and the situation quickly deteriorated: the shortage of staff was exacerbated when workers became infected or, in some instances, refused
TABLE 1-1 Data Depicting the Deficit of Medical Doctors and Hospital Beds in the Ebola-Affected Countries at the Time of the Ebola Outbreak in Comparison to Higher-Income Countries
Medical Doctor Density
Hospital Bed Density
Guinea 0.1 physicians/1,000 population (2005) 0.3 beds/1,000 population (2011)
Liberia 0.01 physicians/1,000 population (2008) 0.8 beds/1,000 population (2010)
Sierra Leone 0.02 physicians/1,000 population (2010) 0.4 beds/1,000 population (2006)
United States 2.45 physicians/1,000 population (2011) 2.9 beds/1,000 population (2011)
United Kingdom 2.81 physicians/1,000 population (2013) 2.9 beds/1,000 population (2011)
France 3.19 physicians/1,000 population (2013) 6.4 beds/1,000 population (2011)
SOURCE: CIA, 2016.
to report to work due to fear of infection; health facilities closed due to a lack of staff or could offer only the most basic care; and, as the number of cases increased, Ebola patients were denied treatment and turned away from facilities (MSF, 2015). As the epidemic progressed, the inability of the countries' systems to control the epidemic became clear. Foreign medical staff and aid organizations stepped in to provide support and direct care. Médecins Sans Frontières (MSF), as one of the few agencies with direct experience responding to Ebola outbreaks in the past, had staff with established expertise in treating Ebola. As a result of its experience, MSF and its staff was quickly at the epicenter of the outbreak (Hofman and Au, 2017). As the affected area and number of infected patients grew MSF staff and resources were soon spread thin (MSF, 2015). Health care facilities often lacked personal protective equipment to prevent transmission to health care workers, and as workers became infected, the facilities acted as amplifiers of the virus (WHO, 2015b). In addition, the treatment units lacked the staff and the equipment to provide the necessary supportive care—particularly intravenous fluids and electrolyte management—and patient demand far outpaced the availability of treatment beds (WHO, 2015b). The opening of treatment centers was delayed by a lack of funding, and patients traveled for miles over poor roads in attempts to get care.
In addition to the lack of facilities, staff, and equipment, the response to the Ebola outbreak was made more difficult because of such issues as stigma, fear, rumors, traditional practices, mistrust of authorities and foreign response workers, and mistakes made in engaging communities and community leaders. Stigma took on different forms in different communities, but it complicated the response efforts in all three countries. For example, in Guinea, Ebola initially spread among the Forestièrs (people from the Forest region), a marginalized and suppressed ethnic group. Guineans from the rest of Guinea initially saw Ebola as a disease of "immoral" people (Fairhead, 2015). As a result, Guineans were slow to admit that Ebola could infect their communities and resisted taking measures that could prevent the spread of the virus (Taddonio, 2015). Also in Guinea, rumors spread that foreign response workers were deliberately spreading the virus through disinfection campaigns or that they were killing people in order to harvest their organs (WHO, 2015b). Traditional burial practices in the region—which include kissing, touching, and washing the body—were responsible for many secondary infections (Manguvo and Mafuvadze, 2015). One traditional healer's funeral, which drew hundreds of mourners from miles around, may have been the source of as many as 365 subsequent Ebola deaths (WHO, 2016c).
The mistrust of authorities—which was exacerbated by a heavy-handed government response which included quarantine, mass cremations, and the use of military force—resulted in community resistance to response
workers (Pellecchia et al., 2015). Authorities often failed to establish effective communication with community members and could not answer their concerns, and the community sometimes did not comply with the infection control efforts of authorities and actually avoided contact with health care facilities or workers (RAS, 2015). Patients who entered Ebola treatment units (ETUs) were sequestered away from the outside world and all too often never emerged except for being cremated and buried safely without the involvement of family. The process, while understandable from a public health perspective, served to drive a wedge between the health system and the community, and the result was disastrous. Patients ran from authorities, or families hid them away, and burials took place in secrecy and without precautions—and transmission of Ebola increased (WHO, 2015b). Community resistance even took the form of violence. For example, in Guinea, treatment facilities and equipment were vandalized, foreign epidemiologists were run out of town by an angry mob, and, in one instance, an eight-member response team was murdered in a village (McCoy, 2014; WHO, 2015b). Nearly 1 year into the epidemic, new cases continued to emerge in both new areas and areas that had already been affected, while communities were overwhelmed by unmet needs—bodies lay uncollected on the streets, patients were dying outside of full treatment units, and orphaned children were left to die (WHO, 2015b).
"Unprecedented" and "Out of Control"
The first victim of the outbreak contracted Ebola in the village of Meliandou in December 2013, and the virus soon spread to the nearby towns of Guéckédou and Macenta and beyond as contacts dispersed to other locations. But it was not until early March 2014 that the Ministry of Health seriously confronted the mysterious spreading illness, and not until March 14 that MSF was asked for help (Baize et al., 2014). Upon learning of the outbreak, MSF quickly sent emergency teams into the field, with the first team arriving in Guéckédou, Guinea, on March 18 (MSF, 2015). Concerned about the likelihood that it was Ebola, MSF arranged to obtain and ship samples for diagnosis to the Inserm laboratory in Lyon, France, where the diagnosis was confirmed and announced by MSF on March 22. In the WHO's first official outbreak report on March 23, the organization reported that the Ministry of Health, WHO, and other partners were taking steps to control the outbreak and that teams had been deployed to search for and manage cases, while MSF actually began to mobilize the capacity to receive affected patients (WHO, 2014b). The WHO country office in Guinea classified the outbreak as a grade 2 emergency: "a single or multiple country event with moderate public health consequences that requires a moderate WHO country office response and/or moderate international
WHO response" (WHO, 2013). However, in late March, a case was confirmed in the capital city of Conakry, 400 miles away from the initial index cases (MSF, 2015). By March 31, MSF declared that the outbreak was unprecedented because of the geographic spread of the cases (MSF, 2014b). One day later, despite the appearance of confirmed or probable cases in Sierra Leone and Liberia, WHO spokesman Gregory Hartl in Geneva downplayed the outbreak, saying that it was relatively small, neither an epidemic nor unprecedented, and that the appearance of Ebola in a capital city was not a new phenomenon (Samb, 2014). MSF continued to warn about the very real potential for a humanitarian disaster, saying that the distribution of cases in Guinea and Liberia showed that the epidemic was already of a magnitude never seen before and characterizing the response of state authorities and international organizations as minimal (Samb, 2014).
By mid-May 2014 the outbreak seemed to be waning: there was a slight decline in cases in Guinea, Liberia had not reported a new case since April 9, and there were no confirmed cases in Sierra Leone (WHO, 2015b). However, the hope that the three-country outbreak was resolving proved to be wishful thinking. On May 26, the first case was confirmed in Sierra Leone, and it soon became clear that the disease had already been present in the country for some time (Williams, 2015). Within 3 days, from May 27 to May 30, the cases of Ebola reported in Sierra Leone tripled from 16 to 50 (Boston Children's Hospital and Harvard Medical School, 2016). There was also an escalation of new cases in Liberia and Guinea, and by late June, Ebola patients were identified in more than 60 separate locations across the three countries (MSF, 2014a). On June 21, MSF declared that the epidemic was "out of control," and it warned that it was reaching the limit of what it could do alone; MSF said it could no longer respond or send teams to new outbreak areas and argued that containment would require massive assistance from local governments and international organizations (MSF, 2014a). On later reflection, MSF director of operations Bart Janssens said that it was like "shouting into a desert" as their appeal for help went unanswered (MSF, 2015). The WHO, the U.S. Centers for Disease Control and Prevention (CDC), and other international organizations sent small numbers of experts to help in the response (CDC, 2016a; WHO, 2014a), but the vast majority of the day-to-day treatment of patients was being provided by local health workers and volunteers from private aid organizations such as MSF as well as by smaller groups such as Samaritan's Purse and SIM (Serving in Mission) (MSF, 2015).
By late June 2014, the West Africa outbreak was officially the largest in history, with 759 confirmed, probable, and suspected cases, including 467 deaths (WHO, 2014d). (See Figure 1-1 for a graphic display of the progression of the epidemic in the three countries.) On July 24, the director-general of the WHO declared the outbreak to be a grade 3 emergency (WHO, 2014c). International attention to the Ebola epidemic was
FIGURE 1-1 Weekly reported Ebola cases during the 2014–2015 Ebola outbreak.
SOURCE: BBC, 2016.
heightened when people from outside the African continent were infected: an American citizen died of Ebola in Nigeria on July 25, shortly after arriving from Liberia; two American aid workers were infected in Liberia in late July and transported back to the United States for treatment; and a Spanish priest died in Madrid in early August after treating patients in Liberia. These cases sparked fears that Ebola could become an international pandemic and spread far beyond the affected region. Yet it was not until August 6 that the WHO director-general convened an Emergency Committee for Ebola under the International Health Regulations (IHR 2005), and it was not until August 8 that WHO declared the Ebola outbreak a public health emergency of international concern (PHEIC) (WHO, 2014e).
International Response
For the past decade, since the adoption of the updated IHR in 2007,1 there has existed a mechanism to engage the international community in a global public health response. This mechanism resides in the responsibility of the director-general to convene an emergency committee to advise on
1 The IHR (2005) entered into force, generally, on June 15, 2007, and are currently binding on 194 countries (States Parties) across the globe, including all 193 Member States of WHO (WHO, 2007).
the need to declare a PHEIC, the most urgent designation for a potentially pandemic infectious diseases threat. A PHEIC is an event that constitutes a "public health risk through the international spread of disease" and that "potentially require[s] a coordinated international response" (Murthy, 2016). Four public health crises have been designated PHEICs since PHEIC was defined in IHR 2005: swine flu (2009), polio (2014), Ebola (2014), and Zika virus (2016) (CDC, 2016b).
The declaration of a PHEIC made clear the need for a coordinated international response, and the global community gathered to aid the individuals in the affected communities and countries (WHO, 2015c). The international response was multifaceted, including pledges of money from foreign governments to help build containment facilities to care for the infected and to build laboratory capacity for diagnosis, and the mobilization of foreign volunteers, including health care workers and public health outbreak control experts to provide patients with the best possible level of care and to stop the epidemic from spreading further. However, not much happened until mid-September, when the UN Security Council passed Resolution 2177 (UN, 2014), calling for the creation of a UN Mission for Ebola, and governments began to mobilize the logistics for support. Shortly afterwards, at the High-level Meeting on Response to the Ebola Disease Outbreak at the United Nations on September 25, 2014, Joanne Liu, international president of MSF, said, "Generous pledges of aid and unprecedented UN resolutions are very welcome. But they will mean little, unless they are translated into immediate action. The reality on the ground today is this: the promised surge has not yet delivered" (Liu, 2014). The WHO coordinated outbreak response efforts through the Global Outbreak Alert and Response Network, which "deployed a multidisciplinary workforce of 895 experts in the current Ebola outbreak response operation in West Africa, including doctors, nurses, infection control specialists, logisticians, laboratory specialists; communication, anthropology and social mobilization experts, emergency management and public health professionals among others" (WHO, 2016b).
Shortly after the declaration of a PHEIC, the WHO began to convene meetings to discuss the use of potential Ebola therapeutics and vaccines that were in various stages of development. ETUs had little to offer patients because treatments such as supportive care with fluids and electrolytes, monitoring blood pressure and kidney function, and medications for associated secondary infections were unavailable, rudimentary, or limited. The lack of targeted antiviral therapeutics meant that ETUs were limited to providing supportive care for patients, and mortality rates were high
(CDC, 2015a). Some patients—primarily Westerners—had been treated with unproven Ebola therapeutics2 and survived, giving hope that a safe and effective therapeutic could be found in time to stem the tide of the epidemic, while rumors circulated in West Africa that there was a magic or secret serum cure that was not being made available for them (Seay, 2014). The WHO convened several meetings during the fall of 2014, during which stakeholders discussed the scientific, ethical, and regulatory issues involved in conducting clinical trials on these therapeutics and vaccines. By December 2014 the first clinical trials began in the region, as the death toll from Ebola neared 8,000 with over 20,000 reported cases (Dunning et al., 2016; WHO, 2014c).
Key players involved in developing and conducting the clinical trials in West Africa included the WHO; research organizations such as the U.S. National Institutes of Health; public health organizations such as CDC and Institut national de la santé et de la recherche médicale3 (Inserm); academic centers including the University of Oxford, the London School of Hygiene and Tropical Medicine, and the Institute of Tropical Medicine at Antwerp, Belgium; humanitarian groups such as MSF, International Medical Corps, and GOAL International; pharmaceutical companies including GlaxoSmithKline, Merck, and Johnson & Johnson (Janssen Pharmaceuticals); and international funders such as the Wellcome Trust and the Bill & Melinda Gates Foundation (WHO, 2015f). There were many hurdles to overcome, and international research groups and researchers worked in partnership with the ministries of health in Guinea, Liberia, and Sierra Leone to implement their trials.
Conducting the trials took immense effort, from selecting investigational medicinal products to identifying trial sites and setting up appropriate infrastructure to implement trials in the midst of a public health emergency. The success of these groups in launching clinical trials on a compressed time frame, in countries that were unfamiliar with clinical research, and for products that had largely never before been tested in humans, was groundbreaking. However, this success was not without setbacks, which included administrative delays (Lang, 2015) and various disputes regarding the selection of vaccine and therapeutic candidates, trial designs, and other issues. The disparate goals and missions of international partners were displayed when conflict arose over two different perspectives regarding the goals of the clinical trials and how best to design them (Presidential Commission for the Study of Bioethical Issues, 2015). Research organizations
2 Unproven investigational therapeutics used under expanded access (also known as compassionate use) included ZMapp, brincidoforvir, TKM-Ebola, favipiravir, and convalescent plasma (WHO, 2015a).
3 France's National Institute for Health and Medical Research.
said that the aim of conducting clinical trials should be to identify safe and effective interventions as efficiently and reliably as possible and that randomized, controlled trials were the best way to achieve this goal. Others said that trials should be conducted in order to provide access to the potential benefits of experimental interventions to as many participants as possible. These stakeholders promoted the use of research designs without randomization or concurrent controls. The conflict between these two perspectives became a central point of contention between stakeholders. These protracted arguments hindered the implementation of robust clinical trials during the 2014–2015 epidemic. (The conflict between researchers and its impact on trial implementation is further discussed in Chapter 2.)
ORGANIZATION OF THE REPORT
This report is organized into six chapters, which follow this introductory chapter. Chapter 2, Conducting Clinical Research During an Epidemic, explores the arguments that arose around clinical trial designs, discusses the ethics and moral principles of conducting clinical research during an epidemic, and examines the ethical arguments made during the 2014–2015 Ebola epidemic. Chapter 3, Assessment of Therapeutic Trials, reviews the formal clinical trials on investigational therapeutic agents conducted in West Africa during the Ebola epidemic, specifically looking at the scientific value of the data generated as a result of the trials. Chapter 4, Assessment of Vaccine Trials, similarly assesses the formal Ebola-specific vaccine trials conducted in West Africa during the Ebola epidemic. Chapter 5, Strengthening Capacity for Research and Response, examines the underlying health systems in West Africa and how a lack of clinical and research capacity influenced clinical research and epidemic response, examines logistical considerations that impacted the conduct of trials, and makes recommendations on how to strengthen capacity to be better prepared for the next epidemic. Chapter 6, Engaging Communities in Research and Response, discusses the social and community context that surrounded the Ebola outbreak and how this influenced clinical trials and explores best practices for community engagement in the event of a future public health emergency. Finally, Chapter 7, Facilitating International Coordination and Collaboration, discusses the need for a coalition of international stakeholders to establish a mechanism that will encourage relationship building and participation of the global research and development and epidemic response communities in addressing key concerns prior to the next epidemic.
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Where Does Telegram Save Files Android
Click on "Show in Folder". (if you already have it organized, great, just make sure you don't copy more files than you have disk space on the phone). Pure instant messaging — simple, fast, secure, and synced across all your devices. It has over 100 million downloads (as on 5-10-2017) on play store and people claim it to be faster and more functional than Whatsapp (fingers crossed). Once you have confirmed that WhatsApp is saving Photos to the Photos Gallery on your Android Phone, you can follow the steps below to transfer Photos From Android Phone to PC or Mac. Download Facebook 243. Step 2: Your computer will recognise the device and ask you what you want to do. No coding skills required. -Find a trusted site that is offering a download link for the APK file. and you can also join Adult Telegram Group And Cricket telegram Group Link or funny telegram group link After Joining These groups You will get. Qbox provides out of box solution for Elasticsearch, Kibana and many of Elasticsearch analysis and monitoring plugins. Right click on "OPEN WITH" link which is located just under of file. How does it work? This flaw, also known as Media File Jacking, arises from the time lapse between when media files are received through WhatsApp or Telegram and are written to the disk — when. Permissions. Starting in Android 6. Press question mark to learn the rest of the keyboard shortcuts. With a user-friendly interface, it allows you to transfer files between Android and PC with previewing, as well as manage (delete/edit/read) Android files in batches on your computer effectively. To Download Telegram For PC,users need to install an Android Emulator like Xeplayer. In this guide, we are using Microsoft Edge browser to save a webpage as PDF but instructions are exactly the same for all web browsers including Google Chrome, Mozilla Firefox, Internet Explorer and Opera. Telegram is a cloud-based messaging app for mobile and desktop. Chances are that you already have them installed. Notifications have been rebuilt from scratch, bringing improved behavior & reliability, new features & customizations, and reduced background battery usage. It's a blue icon with a white paper airplane inside. Facts: Can you recuperate deleted text messages from android phone? The answer is totally yes. You can use it to transfer files between mobile phone and computer or laptop in a fast way. Can't find your downloaded files on your Android phone? Don't worry, we're here to help. The app is very popular among Android and iPhone users because of its features like channels, bots, sharing large files, etc. Uploading and Downloading Files When working with the API, it is sometimes necessary to send a relatively large file to the server. Download WPS Office for Android. To do that, tap on the search icon and search for the word Themes. Open the Telegram desktop app on your computer. Make your Android phone and tablet complete with the easiest to use free and open source BitTorrent and Cloud Downloader app which also includes a file browser and music player. Your One-Stop Solution that Lets You Manage Your Entire Mobile Lifestyle in One Convenient Place. The files are apparently there somewhere, you just have to dig into your Android device's setting to find them. In other words, it is the «Telegram» folder for smartphones and the hard disk drive folder chosen by a user for PC. Open gallery and the file will be visible in the telegram folder. Users can send messages and exchange photos, videos, stickers, audio and files of any type. The Press-Telegram is the local news source for Long Beach and the surrounding area providing breaking news, sports, business, entertainment, things to do, opinion, photos, videos and more from. As long as you know this person's. after completing your back up you can import the created. Obviously you'll have to enable shared folders on your computer, which you can do from the option in the Network section of the Windows explorer. 1 and port to 8080 and you have successfully bypassed the firewall. If you deactivate or delete your telegram account, all your messages, groups, channels, contacts will be removed. For example, when sending a message with a photo/video attachment or when setting the current user's profile picture. T here are lots of applications available on the internet on a particular thing but how to choose best one among them? Therefore, today we will be sharing the top best Android data recovery apps/tools 2019 that will help you to recover deleted files on Android. There are several methods for android file transfer for Windows users. Here's how to do it. As all your messages are held in the cloud,. When a file is available offline, you can access that file even when your phone isn't connected to Wi-Fi or data. But, to reduce mobile data usage, the app has settings to disable for specific media types or as a whole. Now navigate to the folder containing the vCard file and select it. To run the app from Android studio, open one of your project's activity files and click Run icon from the toolbar. Launch android_root. This will load it into the Safeguard Viewer Downloads folder. Open the Telegram app. save file extension include temporary saved files that are created by the Nano Unix text editor, Salt Lake city 2002 game files, game files saved for the Prey video game and game files that have been saved for the Doom 3 video game. It's the blue circle with a white paper airplane. To save your Facebook app to your Android's SD card, go to your Android's settings and open your applications manager. As long as you know this person's. On the desktop, apps like Dropbox and Google Drive sync folders between your devices. However, you must write the code to actually write the files to disk. You only have to connect your phone and let the software do the rest of your job. the functions for writing text, binary or ini files will create a new file in the save area if one does not already exist, copying over any information from the original files included with the game bundle. To use these hidden flags, you need to do things such as turn on Developer Options. Although I cannot email the file to myself, I can install the sd card in a usb adapter, and plug it into my computer, put my file on that. Then, you are going to see an. You need to receive notifications from your device Remote Bot can notify you about notifications from your device with ability to answer. Post code examples, ask for input, and share your opinions with fellow devs!. iPhone and Android phones show new text messages by default as a notification on the lock screen. Note: It is assumed that you already have WhatsApp installed on your Android device. WhatsApp and Telegram allow users to choose if they want to save all incoming multimedia files on internal or external storage of their device. With a simplified interface, large buttons, and powerful voice actions, Android Auto is designed to make it easier to use apps that you love from your phone while you're on the road. Since Telegram's launch in 2013 , you can send files up to 1. Adobe Reader and Acrobat products try their best to open even such PDF files but they do differ in terms of the kind of such pdf files they are able to open. Click on Save file and wait until the end of the download. This thread is all about running Google apps on your Blackberry 10 device. Android Development. From Google Play, if your device supports it (recommended) 2. The solution is to do an adb uninstall of the app that won't update but then the app data will not persist. The source code is published under GPLv3 with OpenSSL exception, the license is available here. 0 for Android. Cocospy is a useful and reliable tool for hacking Telegram. For Android app files, select My files Play files. Because the actual paths to internal and external storage may vary from device to device or from Android version to Android version, it is not recommended to hard code the path to the files. Download the APK file of TeaTV from the official website USING PC or a laptop and save it in your Dropbox or Google Drive folder on your PC On your Android TV, go ahead and fire up ES, then scroll down to the "Network" section. ) Android 9 also brings important improvements that protect all web communications and offer private web surfing. One must set up a PIN or password for the Telegram app first on Android in order to be able to have the choice to take screenshots in Secret Chats. What you can do with App Backup & Restore? – Bulk Backup & Restore apps that not used frequently to save more space – Auto Backup & Restore multi-versions to avoid unnecessary. Download and run WazzapMigrator on your Android phone. The second option allows you to save the recoverable files back to the local device (to the internal memory or SD card of the same device from which the files are being recovered). 2)After Downloading the file just go to Google Chrome Extensions,you can go to Google Chrome Extensions by pressing Ctrl + H it will open up browser History. An app called FolderSync lets you sync files and folders to and from your Android phone, just like Dropbox does on the desktop. Using Telegram Web. Click more. Users set up accounts with a phone number and can use the app on all platforms. Bringing Office Lens to iPhone and Android is a significant step for extending OneNote capture capabilities to more devices and endpoints. Telegram is a cross-platform cloud-based instant messenger with a focus on security. db in the app's "files" folder:. Telegram is a specially designed messaging app that works smoothly with Android, iOS and Windows smartphones. 3 aka "Gingerbread" Application Framework running on top of Playbook/BB10 OS and Libraries ► Enables Android apps to be installed and run inside it ► Deep integration with BB native framework with the objective to make Android app indistinguishable from native apps Application Framework. 5 , whenever you send multiple photos or videos they are grouped into albums. If it is an Android device, you require quick physical access to it while for Ipads and Iphones, set up can be done remotely. Multi-media files are saved in the external SD card and you can easily transfer data from a. With these downloaded windows 10 apps you can transfer and install them in any phone you want. Telegram Cloud is a tool which offers free unlimited online storage and makes uploading your files as simple as sending a message on Android and iOS. i dont know what programme to use to save the files or if i have to buy something like winzip or if i can use someting thats already on my pc. By cleaning out a few things, you gain space for. Drag and Drop of a file, APK, or flashable zip file does not work. ES APP Group. Manually installing the APK files for BlackBerry apps (option 2 above): If an Android app cannot be downloaded through Google Play, or a user desires to install an app outside of Google Play, the app's APK file can be downloaded and installed through a web browser on their Android smartphone or tablet. It's usually on the home screen or in the app drawer. The JavaScript Object Notation file type, file format description, and Mac, Windows, Linux, and Android programs listed on this page have been individually researched and verified by the FileInfo team. Nowadays it is definitely a necessity. Using Telegram Web. Press J to jump to the feed. Click Join community in the upper right-hand corner. Save new files from Google Drive to Telegram channel. It's the blue icon with a white paper airplane inside. Users can send messages and exchange photos, videos, stickers, audio and files of any type. Getting a file from your Android smartphone or tablet to your PC might not seem easy when you first try, but there are a number of quick methods to do it. Edit apps and customize them however you want. Telegram is the fastest messaging app on the market, connecting people via a unique, distributed network of data centers around the globe. * Add grid view. Benefits of using Cocospy to hack Telegram. MyFiles is a file manager. Now, all your lost data can be safely retrieved and you're definitely the only person who can access them. It's usually on the home screen or in the app drawer. It appears in a list of Bluetooth Inbound Transfers. Find the letter from your Android phone. By the way, if you want to manage iPhone data easily, you can have a try on AnyTrans , which can help you transfer data from computer to iPhone and vice versa. Download Telegram MOD APK App for android and windows Desktop. For those who don't know what Telegram is, it is a messaging app, very much like WhatsApp. The file is sent from your Mac to the Android tablet. In the case of WhatsApp and Telegram, if users enable the "Save to Gallery" setting (enabled by default in WhatsApp), the application will save incoming media into the Android file system's. I'm trying to get all Telegram contacts to use in my application ,here is my code : Cursor c = getContentResolver(). NET idioms for file access. Now, Telegram covers almost all known platforms, which means that you can find Telegram for Android, iPhone, iPad and Windows Phone, a web version and even desktop applications for Windows, MacOS and Linux. How does it work? This flaw, also known as Media File Jacking, arises from the time lapse between when media files are received through WhatsApp or Telegram and are written to the disk — when. If you simply save your image to Camera Roll like you always do, the pic will be static and won't move. Open Telegram on your Android. Start a secret chat. In this demonstration, we'll use an app called Status Saver for WhatsApp. The method of determining a storage location for such files is analogous to the previous variant. From the Amazon App Store (for Kindle tablets and Android devices with the Amazon app) 3. Apps to easily encrypt. Search Microsoft Flow See what's new in the October 2019 release. On Android, this currently works with supergroups and channels (just tap and hold in the chats list, then 'Delete from Cache'). [issue]:can't download any file so as tittle say, i can't get any file in the android client, it's updated to the last version, i tried to reinstall and even factory reset my moto g2, still when someone sends me a picture it keep "downloading". Nice Trick, Check it Out! There is no provision to share any other file from the Android file system like a Word or a PDF. Pure instant messaging — simple, fast, secure, and synced across all your devices. Also specify the path where you want the export to be saved. @tgx_android April 25, 2019 Telegram X: April Update @tgx_android. According to the researchers, WhatsApp saves files to external storage automatically, while Telegram does so when the By Chakri Kudikala July 16th, 2019 AT 11:23 AM Apps. Select Export Telegram. … File object representing the directory name in the internal storage, creating the … Saving data to a file in your Android application - Cindy Potvin […]. To use these hidden flags, you need to do things such as turn on Developer Options. To save a file using Thoai Media – Open the website > Paste the URL of the file > Click on the service where the file should be saved > Authenticate. It is used as the best alternative to WhatsApp due to its amazing features. Most of the solutions are good to. This will save you from fumbling around on your mobile phone's keyboard to try to arrange, categorize, create, edit, and delete those contacts. The second option allows you to save the recoverable files back to the local device (to the internal memory or SD card of the same device from which the files are being recovered). Telegram is a messaging app with a focus on speed and security. Apps to easily encrypt. T here are lots of applications available on the internet on a particular thing but how to choose best one among them? Therefore, today we will be sharing the top best Android data recovery apps/tools 2019 that will help you to recover deleted files on Android. Just go into Settings and toggle Save to gallery off. It's the blue icon with a white paper airplane inside. mht) file into a Save Page WE (. The first thing to note is that you do not need a Scansfer account if you're using the Phone to Phone, or Computer to Phone functions (Computer in this case means any type of computer). Remote Bot for Telegram is a compact application with wide capabilities for remote management of Android devices via Telegram Usage examples: 1. Albums, Saved Messages and Better Search Starting with Telegram 4. Note- Sometimes your. User Interface Learn about the complete set of user interface control widgets available for Android. fone - Transfer (iOS), you can transfer music and voice memos from iPhone X/8/7/6S/6 (Plus) to computer in 3 simple steps. The Android runtime in BB OS 10. Files you've downloaded, photos you've taken, as well as data stored by apps, are major contributors to unnecessary clutter on your Android device. When u install "File Expert" App this app will add "Save to" plug-in to your players list when you want to play a video in Telegram u must choose "Save to" instead the player and Save the video in ur desired Folder This new Telegram app is more Different from before and more secure for the record. This is the complete source code and the build instructions for the alpha version of the official desktop client for the Telegram messenger, based on the Telegram API and the MTProto secure protocol. Run free online Android - Snapchat. Root your phone with one click. This wikiHow teaches you how to download videos from a Telegram chat to your Android phone or tablet. The method of determining a storage location for such files is analogous to the previous variant. Telegram is a messaging app that offers end-to-end encryption and also offers a ' Secret Chat ' feature, that self-destruct messages after the. Update: Telegram Desktop version 1. Sometimes when you connect an Android phone to a PC, the computer don't show the files on the phone. Navigate to the Vault List from the main menu. How do I open the files and chat history I downloaded from Skype? The downloaded messages and files are delivered in a. the file system functions will return information on files from both the bundle and the save area, but will only write to the save area. Hoverwatch android phone tracker has a very important feature — it can track Todo list. Open Telegram on your Android. The advantage to this method is that you can keep using Android and don't have to reboot to perform the backup, but other than that it does essentially the same thing. Our goal is to help you understand what a file with a *. Vidmate is one of the best known applications currently available for downloading videos and songs from online services like Vimeo, Dailymotion, YouTube, Instagram, FunnyorDie, Sex Video, Vine, Tumblr, Soundcloud, Metacafe, and tons of other multimedia portals. Temporarily Banned. TELEGRAM MESSENGER is a text-, image-, video-, and file-messaging program that securely routes all communications (except for group messages) through encrypted servers in the cloud. Launch File Manager App on your device. The software interface consists of two parts, the left will show document chapter directory, the right is a browser to show document content. DannyM93, Mar 20, 2018: That's a feature of the app. Whenever you want to upload an image, there will be two ways to do it: gallery and files. Next to the file's name, tap More Download. At the moment mp3s are displayed as voice messages. To save your Facebook app to your Android's SD card, go to your Android's settings and open your applications manager. 2-Just download a video ( Just video or a file ) not picture or voice ! 3-Lunch File Explorer and open recent part. Left – Android, Right – iOS. iPhone doesn't support moving images. Android Android 9 Pie. The emulator uses ADB. Wally, who had suggested having the city consider changing the date of trick. Offcloud is a decent service which allows you to upload remote files on Google Drive. It is now a valuable resource for people who want to make the most of their mobile devices, from customizing the look and feel to adding new functionality. Open your phone's Settings app. After you download the file > Tap on three vertical dots in top-right corner of that file > Tap Save to Downloads You will get the file with original filename in. How to Reopen, Close and Save project in Android Studio. Save 60% on our. Tip: If you're going to create a new file, based on an existing file, but only want your changes saved in the new file it's a good idea to do the Save a Copy process before you've made any changes. Just go into Settings and toggle Save to gallery off. Also there is unRAR license restriction for some parts of the code. Telegram download and installing on your pc is completely similar as installing other softwares on the pc. In the General panel, go to the Downloads section find the Downloads section under Files and Applications. Other versions of Android 4. In this post, we will tell you how to use Telegram stickers in WhatsApp for Android. This wikiHow teaches you how to pin a Telegram chat to the top of the list when you're using an Android. Telegram Messenger has been available on multiple platforms for years now, including Android, iOS, Windows PC and Windows Phone. The newly updated chat app has introduced a silent. If you decline to agree, the app is not installed. Android's user-visible file system is one of its advantages over iOS. If you select to download an image Telegram Web opens a dialog where you can freely choose the storage location. Nice Trick, Check it Out! There is no provision to share any other file from the Android file system like a Word or a PDF. The JavaScript Object Notation file type, file format description, and Mac, Windows, Linux, and Android programs listed on this page have been individually researched and verified by the FileInfo team. Step 4 Import iCloud Contacts to Android Contact book. Manually installing the APK files for BlackBerry apps (option 2 above): If an Android app cannot be downloaded through Google Play, or a user desires to install an app outside of Google Play, the app's APK file can be downloaded and installed through a web browser on their Android smartphone or tablet. Telegram for Android has now reached version 5. Just click "Next" button to analyze data from Android phone/tablet. Bitstrips. selecting save, It will auto create telegram folder in gallery if it is the first one. Security firm Symantec has found a vulnerability in WhatsApp and Telegram's Android apps which could let hackers intercept and alter files sent between users, such as photos, documents, or videos. Xender to copy files from your phone to your PC. Vidmate is one of the best known applications currently available for downloading videos and songs from online services like Vimeo, Dailymotion, YouTube, Instagram, FunnyorDie, Sex Video, Vine, Tumblr, Soundcloud, Metacafe, and tons of other multimedia portals. If a vault save file exists, you will receive a message prompt stating that there is a save conflict. Or if you prefer, you can also share files directly from Dropbox. May 26, 2014 … Each application has its own private internal storage to save files. If you ever missed that feature and wanted to download APK files from the Google Play, there's now a very handy way to do that. json file to configure your application to use Firebase. Then I want the same file to return the inputted text in String form and save it to another String which is. Telegram is based on the MTProto protocol. How to Pin Posts on Telegram on Android. An app called FolderSync lets you sync files and folders to and from your Android phone, just like Dropbox does on the desktop. ico suffix is and how to open it. From that day on, not only can human use Telegram, so can machines. This wikiHow teaches you how to download a video from a Telegram chat and save it to your computer, using Telegram's desktop app. , which bedevils you a lot. It is a popular activity to save files from your Android phone or Android tablet to a cloud storage tool, such as OneDrive, which allows you to access your Android data anytime and anywhere even without the Android device in your hands. Open Telegram on your Android. Games still reign king in the Android catalog in 2018. One is normal chat and other is secret chat. Open Contacts app on your Android phone and tap Menu button. So if you change location of that picture or rename it, you see that telegram needs to download your sent picture. Post code examples, ask for input, and share your opinions with fellow devs!. TDLib supports all Telegram features and makes developing Telegram apps a breeze on any platform. App settings combined with Android behavior can put data integrity at risk for WhatsApp and Telegram Telegram uses external storage for its "Save to Gallery" feature. How to Reopen the project in Android Studio perform the following steps: Step 1: Firstly, Click on File then Click on Reopen Project and choose the file which file you want to be opened. The xml layout contains an EditText to write data to the file and a Write Button and Read Button. Common uses for the. Telegram client apps are available for Android, iOS, Windows Phone, Windows NT, macOS and Linux. ► It's Android Open source v2. Note: As of Android Studio 2. Telegram has many features that are hard to find in other instant messaging apps. Once again, this app is here to simplify your Facebook experience by providing all your favorite features from one. One easy solution is to enable 'Save to gallery' from the settings. Telegram Android latest 5. Note Call Recorder. 0, Android supports adoptable storage, which is provided by physical media, like an SD card or USB, that is encrypted and formatted to behave like internal storage. In order to get rid of this stubborn data, you can very well use this option. Download Telegram for PC. You can see "Connected" in the lower-left corner when the software connecting your device successfully. PWA manifests include its name, author, icon(s. How to Recover Deleted Files from Android By Emily Watson , Thursday, Octorber 11, 2019 Sometimes you can delete files that you actually need on your Android phone, such as photos, downloaded MP3 audio files, contacts, messages, etc. Programs like this can transcribe live, spoken words into text, and Dragon is one example that can even do it with an audio file. The final Word and PowerPoint documents are real Microsoft Office documents. Telegram is a specially designed messaging app that works smoothly with Android, iOS and Windows smartphones. Get Move to iOS from Google Play If you live in China mainland, learn how to download Move to iOS. When you have Save Original Photos or Save Original Posts turned on, every photo you post on Instagram will also be saved to your phone's library. I want to save music on iPhone 6s that is downloaded from Telegram. Using Scansfer. CONTENT_URI,. exe to facilitate file transfer when you drag and drop a file onto the screen. iOS 11 has a much improved Save to Files. Some apps store their save games/configuration data files on /sdcard/APPNAME/ , or just on the /sdcard/ To be able to use root apps, you'll need to have rooted your Android device and have given permission from one of the superuser apps. This will take you to the standard Android folder picker that you can use to select the folder into which the files will be saved. The latest update revamps notifications and the account manager. , end- to- end encrypted with no possibility of Telegram seeing the message contents). TeleSign is usefull for Telegram Bot Owner and Crypto Signal Provider / Trader to know current Crypto Rate and Guess Trading Information. These references can then be used to upload or download data, get or update metadata or delete the file. By this way you'll be allowed to access telegram folder like Android and access to videos and pics that are downloaded but not saved. According to the researchers, WhatsApp saves files to external storage automatically, while Telegram does so when the "Save to Gallery" feature is enabled. Pure instant messaging — simple, fast, secure, and synced across all your devices. From the option list, select Import from SD card. Sorry but your browser does not support some of new HTML5 features! Try using latest version of Google Chrome or Firefox. Hackers execute this Spyware Via commands and its used message-exchange protocol of the Telegram online messenger. If it is an Android device, you require quick physical access to it while for Ipads and Iphones, set up can be done remotely. This creates two blank files, one for specifying the gems you'll need and one where the bot's code will live. It used to save them as Adobe files, and I have the latest Adobe reader. Admin can create free or Premium Plan. If Import chat history does not appear, you won't be able to import chat history saved on an SD card or LINE Keep. The xml layout contains an EditText to write data to the file and a Write Button and Read Button. For more information about OBB files, see OBB Support. How do I clear my recent emojis on Android without clearing learned words? I think iOS feature would be great in Android, wouldn´t it? Português do Brasil. APK Editor is an app that lets you do exactly what its name indicates: edit any APK saved to your device. You mentioned that your friends are able to open up the same PDF file on their Android devices. Telegram on Android, Mac OS X, Windows and Linux do not give this option to user, as far as I know. Files are stored in the folder "Telegram Desktop" in your downloads folder on Windows. SMS Organizer helps you complete important tasks by guiding you to the right webpage/app at the right time. When you use your Android device, all the changes you make in your Office apps are now saved automatically, so you never have to press the Save button again. How to Export Telegram chats. Android Contacts Recovery may help you a lot to retrieve deleted/lost contacts from Android phone memory or SIM Card. Tap next to Save Original Photos (iOS) or Save Original Posts (Android) to turn it on. Offcloud is a decent service which allows you to upload remote files on Google Drive. Files you've downloaded, photos you've taken, as well as data stored by apps, are major contributors to unnecessary clutter on your Android device. Click to enlarge Android Transfer Software - Droid Transfer is a Windows application which works alongside a free Transfer Companion app for Android, allowing you to transfer SMS and MMS Messages from your Android Phone to your PC via a USB cable or over your local WiFi network. Infinite Online Videos. SYNCED: You can access your messages from all your devices at once. Here's the steps to access the media files and making them visible in the gallery folder , thus enabling to share or send those files. Home Forums Android Discussion Android Apps & Games Instagram: Direct Message not showing some messages Discussion in ' Android Apps & Games ' started by BigBug , Jan 9, 2016. To do that, tap on the search icon and search for the word Themes. • If you previously used tasks in BBM Groups, you still have access to those tasks in BBM. If you haven't already done so, you might find it helpful to review the Saved Games game concepts. Android Package Installer is a simple lightweight GUI tool to install Android APKs from your Windows, Mac or Linux Computers directly to your Android phone or Tablet. For instance, you can share audio, photos, videos and various other types of files. Begin to Backup Android Contacts to Excel. Now come to the Desktop. Connect your Android to your Windows PC using a USB cable. Some manufacturers do pre-install their own more powerful file managers on Android devices. Press J to jump to the feed. 16 PROJECT MOVED! The code above is older (base) version! The links to the latest and constantly updated public version are below:. Telegram is a specially designed messaging app that works smoothly with Android, iOS and Windows smartphones. Open Files. A fast and - most importantly - secure instant messenger. smartphone or tablet)? hold down at once Volume Down: and Power: for 1–2 seconds = The screen flashes white. Choose from over 4,100 Android app templates. That way your original file will remain unchanged and all your edits will be in the new copy. and paste to Android/OBB folder or Android/Data. Once done, you can now open Grand Theft Auto San Andreas mod apk game and begin playing it. Android Pie supports Private DNS, which uses DNS over TLS to secure your queries. Preview photos, display one-off sites and save your important data at full security!. For example, when sending a message with a photo/video attachment or when setting the current user's profile picture. Here's how it works. The advantage to this method is that you can keep using Android and don't have to reboot to perform the backup, but other than that it does essentially the same thing.

redpajama_set_name: RedPajamaCommonCrawl


Lexalytics is proud to have sponsored the Sentiment Analysis Symposium in New York earlier this month. SAS featured both speakers and workshops aimed at keeping up with sentiment analysis technology and discovering the business value in opinions, emotions, and attitudes. Speakers included representatives from Verizon, Instagram, Bottlenose, as well as our very own CEO, Jeff Caitlin, who spoke on the importance of accurately parsing syntax.
There are three important components to consider when analyzing text to determine its meaning.
-Semantics: The definition of a word depending on syntax and context.
-Context: The circumstances surrounding the text, including the speaker, what they've said in the past, and in what particular space they are speaking.
-Syntax: The effect of sentence structure on the meaning of a word or phrase.
The ability to parse syntax correctly is vital for accurate sentiment analysis. It's not enough for a program to simply weigh individual words for their sentiment. Sentences can contain several different entities towards which different sentiments are being expressed, depending on how the sentence is ordered.
Apple was doing bad until Steve Jobs returned.
Because Apple was doing bad, Steve Jobs returned.
Apple was doing bad because Steve Jobs returned.
To a machine, there are many logical ways for parsing syntax that simply don't make sense to a human. For example, the sentence "John went to the store for milk", might be interpreted as John going to the "store for milk" or milk store, as opposed to going to the store with the intent to buy milk. Humans automatically interpret the sentence as meaning the latter, but machines don't.
Since humans naturally parse syntax, the best way to ensure sentiment analysis software will parse syntax appropriately is to learn like a human. To learn more about parsing syntax accurately and what that entails, check out Jeff Caitlin's presentation below.


text:
AIADMK, BJP seal pact for Lok Sabha elections in Tamil Nadu, Puducherry
Addressing reporters after the meeting, Union Minister Piyush Goyal said the BJP will contest in five Lok Sabha seats as part of the "mega alliance" in Tamil Nadu, which has 39 Lok Sabha seats.
By: Express Web Desk | New Delhi | Updated: February 19, 2019 10:04:00 pm
Union Minister Piyush Goyal said the BJP will contest in five Lok Sabha seats as part of the "mega alliance" in Tamil Nadu, which has 39 Lok Sabha seats. (Source: ANI/Twitter)
The AIADMK and BJP on Tuesday stitched a pre-poll alliance in Tamil Nadu and Puducherry for the forthcoming Lok Sabha elections.
Addressing reporters after the second and final round of discussions by the two parties, Union Minister Piyush Goyal said the BJP will contest in five Lok Sabha seats as part of the "mega alliance" in Tamil Nadu, which has 39 Lok Sabha seats. Puducherry, on the other hand, has one parliamentary seat.
BJP to contest in 5 seats in AIADMK alliance – Honourable Deputy CM Thiru O. Panneerselvam Announces.
— AIADMK (@AIADMKOfficial) February 19, 2019
He also said that the saffron party will back the AIADMK in the bye-elections on 21 assembly seats in the state. "We will support AIADMK in the bye-elections on 21 assembly seats in Tamil Nadu. We have agreed to contest elections in the leadership of OPS and EPS in the state and under the leadership of Modi Ji in Centre," said Goyal, the BJP's election-in-charge for Tamil Nadu.
ALSO READ | 2019 Lok Sabha polls: Ramadoss gets 7 seats as AIADMK seals pact with PMK in Tamil Nadu
The announcement came hours after the ruling AIADMK announced a poll alliance with the Pattali Makkal Katchi (PMK) as part of putting up a broad-based front to face the coming elections. Announcing the tie-up in the presence of Chief Minister K Palaniswami, AIADMK coordinator and Deputy Chief Minister O Panneerselvam said PMK would contest in seven Lok Sabha seats. It was also decided that the PMK would be allocated a Rajya Sabha seat.
Having failed to make significant electoral gains in the southern states barring Karnataka, the BJP needs alliances to pull votes in the region in an effort to return to power at the Centre.
The upcoming Lok Sabha polls is the first major electoral battle for the AIADMK after the demise of its charismatic leader Jayalalithaa in December 2016.
For all the latest Elections News, download Indian Express App
E K Palaniswami
O Paneerselvam
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Give your living room a stylish foundation with this beautiful L Shape Leather Sofa. It features a soft, luxurious feel, while the solid feet give it balance and stability. With a mix wood structure and leather and fabric upholstry, this piece makes for an ideal addition to any decor type.


text:
XXV Чемпіонат України з боксу серед чоловіків — головне змагання боксерів-любителів в Україні, організоване Федерацією боксу України, що відбувається з 16 по 20 листопада 2016 року в Харкові на базі ХТЗ, а півфінальні та фінальні бої у Палаці спорту «Локомотив».

Розклад

Медалісти

Чемпіонати України з боксу
2016 у боксі
2016 в українському спорті

redpajama_set_name: RedPajamaWikipedia


What if my child swallows the toothpaste?
I have a different toothpaste, can I use it with quip?
When can my kid start to use fluoride toothpaste?
Why is the toothpaste watermelon flavored?
What is the flavor of your toothpaste?
Does your toothpaste use sodium lauryl sulfate (SLS)?
Is your toothpaste formulated for sensitive teeth?
Do you offer whitening toothpaste?
Our toothpaste is designed to be mild, fresh, and safe for everyone to use, but it is not made with ingredients specialized for sensitive teeth. Of course, we do encourage you to try it out, but if you find that it's not suited to your needs you can always email us and we will help you change your plan so you can use your own paste.
Does your paste use fluoride?
What are the numbers stamped on top of my toothpaste tube?
How long will a tube of toothpaste last?


Sears Home Services of Waterloo, IA fixes nearly any appliance, no matter where you bought it!
You read that right! No matter where you bought your appliance, Sears Home Services of Waterloo can fix it. We repair the major brands, makes and models. In fact, Sears Home Services has been fixing appliances since 1956.
Whether your refrigerator isn't cooling properly or has another problem, our skilled Sears Home Services' technicians in Waterloo will diagnose quickly and repair efficiently.
Is your washing machine not spinning or your dryer not heating? Sears Home Services in Waterloo offers dependable washing machine and dryer repair services for these and other less common issues.
Heating and cooling unit breakdowns can be a real nuisance. Rely on Sears Home Services in Waterloo for heating and air conditioning repairs that will restore comfort to your home.
What repair can Sears Home Services of Waterloo help you with today?
Sears Home Services in Waterloo also provides other types of repairs including small appliances, riding lawn mowers, exercise equipment and more.
Get started now! Call to book an appointment today. The Sears Home Services technicians in Waterloo can repair your problem—satisfaction guaranteed!
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This week on DVD, we've got a summer movie that belly-flopped at the box office, a couple of smaller Certified Fresh films, some family viewing from Disneynature, and a whole bunch of good TV. Read on for the full list.
Tahar Rahim and Emmanuelle Seigner star in this French drama that weaves together three seemingly unrelated stories that are all connected by a single organ transplant. It comes with an interview with director Katell Quillévéré.
Ben McKenzie and David Mazouz star in this DC Comics-inspired series about the early days of Bruce Wayne, James Gordon (before he became Commissioner), and several classic Batman villains. The season 3 set comes with Gotham's 2016 Comic-Con panel, a look at the new villains, deleted scenes, and more.
Disneynature's annual Earth Day offering for 2017 centers on three animal families — pandas, golden monkeys, and snow leopards — living in the titular nation. Extras include inside looks at how the camera crews captured the rare footage, a music video, and a call to get involved in nature conservation.
Jodie Comer and Essie Davis star in Starz's sequel series to The White Queen, which follows Queen Elizabeth's marriage to Henry VII and the ensuing tensions between their families. Unfortunately, the season set does not appear to come with any extras.
The fourth and final season of this Starz prequel series to Robert Louis Stevenson's Treasure Island finds Captain Flint (Toby Stephens) battling to prevent the extinction of pirates in the West Indies. The season set includes episodic recaps and making-of featurettes, a behind-the-scenes look at production, and a few brief discussions between the cast and crew.
Rachel Weisz and Sam Claflin star in Roger Michell's adaptation of the Daphne du Marier mystery about a young man who becomes obsessed with the cousin he suspects of murdering his guardian. Special features include deleted scenes, a handful of promotional and making-of featurettes, and a commentary track.
Dwayne Johnson, Zac Efron, and Alexandra Daddario star in this big-screen adaptation of the popular 1990s TV show about a group of lifeguards who uncover a criminal mystery and attempt to solve it. Extras include introductions to the cast and characters, a profile of the show's legacy, a look at the stunts and training undergone by the cast, and deleted and extended scenes.


Used skilfully, emails are a great way to reach existing and potential customers in a targeted, organized and non-intrusive way.
People are on the lookout for expert advice and emails happen to be a great way to give it, as well as draw attention to a brand. According to a study by the Direct Marketing Association, email marketing generates an average ROI of $40 for every $1 spent and is used by almost every advertiser/business across the globe. Email marketing comes with several advantages; easy to create, easy to track, and easy to share, plus they have a global reach and can be focused on target prospects in target markets. But more important to most marketing executives, it is the most low-cost marketing technique available to companies.
An exhaustive prospect database, inclusive of email IDs, is the most important asset for any marketer. Here are ways in which you can augment your target list.
1. Opt-in forms: Prospects come from different backgrounds, it is therefore important to capture their requirements. A complete Opt-in form connected to your CRM can help keep valuable information on your website visitors. Make sure the form is short and simple. Ask for the bare minimum as no professional has the time to fill a lengthy form just for the sake of your marketing needs. Supplement the missing information by outsourcing to a company that provides these services.
2. Free trials, offers and reports: Content doesn't always have to be long blog posts. High quality giveaways and trials, work just as well in collecting valuable information.
3. Newsletter subscriptions: Newsletters shouldn't just be about marketing your product, it should offer value to the receiver, whether they choose to buy or not. For instance a photography related newsletter offers tips, tricks and top photographs apart from camera deals and other marketing campaigns.
4. Free Downloads: Free downloads are a great way to increase your database. For instance, if you have been able to create a great gaming app, visitors/customers would love to exchange their email information in exchange for a free download.
5. Buy email lists: There are several service providers who sell database. Magazines and job-search websites have a huge database of information that can also be used by marketers.
6. Events or trade shows: Some companies organize trade shows and events to bring in a crowd. When people register to be a part of the event, the company is able to generate a huge database depending upon the popularity of the event. If you are looking for a young demographic, organize a music show. If you are looking for an executive class demographic, go for a trade show.
7. Blog content marketing: Interesting blogs motivate visitors to return to the site and subscribe to feeds. They will be glad to join your email-marketing list to periodically gain access to great articles.
8. Guest blogging opportunities: Alternatively, you can engage the audience by asking them to blog on your behalf. Depending upon the product category/campaign, there will be many who will voluntarily sign up to post their views and comment on posts.
9. Pop up box: While pop-up boxes are irritating, some can really get the attention of the end user. Make it interesting enough for the viewer to get curious and ask for more.
10. Social media marketing: Spreading creative and unique information on social media is perhaps the best way to gain attention of certain demographics. Today, a majority of people who could be your customers are on LinkedIn and Facebook. Generate curiosity and you will augment your prospect list in no time.
11. Word of mouth: While a bit more difficult than other alternatives, word of mouth can indeed be a strong marketing method. A visitor influenced by word of mouth will share his contact information and is more likely to do business with you.
12. Tele-calling: Politely make prospects a compelling offer, gauge their interest in your product and ask if they would like to receive periodical updates. You will certainly receive many positive responses if this is done well.
1. Don't over-send mails. Be regular so prospects remember you – make them wait for your updates!
2. Check and update your prospect list from time to time.
3. Create distinct lists for different marketing campaigns – segmentation helps in targeting.
4. Design your emails and newsletters – each piece should look good as well as provide relevant information.