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Respiratory Airway Infections
General Goal: To know the cause(s) of these diseases, the most common modes of transmission, and the major manifestations of these diseases.
1. recite the common cause(s), the common means of transmission, and identify the major disease manifestations.
2. determine based on clinical manifestations if a patient has one of these diseases as well as determine which disease they have acquired.
3. explain what is in the vaccines and why it is important to give the vaccines to people.
4. define the difference between shift and drift in Influenza viruses.
5. describe how to avoid getting the various diseases if any prevention means are possible.
Lecture: Dr. Neal R. Chamberlain
Bronchitis, Bronchiolitis, Influenza and Pertussis
The respiratory airways discussed in this section of the handout include the airways from the bronchi to the bronchioles. The infections discussed are acute bronchitis, bronchiolitis, influenza, and pertussis. All of the diseases discussed in this chapter, with the exception of pertussis, are usually caused by viruses; pertussis is caused by bacteria.
I. Acute Bronchitis
Acute bronchitis causes inflammation of the trachea and bronchi but does not involve the alveoli; it is usually caused by viral agents. Acute bronchitis occurs in patients of all ages but is most common in young and older persons. Chronic bronchitis, which is not discussed here, occurs in adulthood.
Viruses are the most common cause of acute bronchitis. Acute bronchitis can be caused by the following agents.
Respiratory viruses that infect the upper respiratory tract: Influenza viruses A and B, parainfluenza viruses, adenovirus, respiratory syncytial virus, herpes simplex virus, rhinovirus, coxsackievirus groups A and B, and echovirus.
Chlamydophila pneumoniae
Manifestations of bronchitis include a cough (which is nonproductive at first but can become mucopurulent), substernal pain, and fever (38.3–38.9°C). Physical findings will reveal an infected pharynx; rhonchi and moist crackles can be heard upon auscultation. Several hours before symptoms of bronchitis develop; the patient will experience malaise, headache, coryza, and sore throat. Chest radiographs do not reveal consolidations or infiltrates, as seen in patients with pneumonia; therefore, a chest radiograph can be helpful in differentiating bronchitis from pneumonia.
Acute bronchitis usually occurs after a previous upper respiratory tract infection with extension of the infection to the bronchial tree.
It is most common in the winter months, similar to most other respiratory diseases.
Air pollution increases the number of cases of bronchitis.
Acute bronchitis is a self-limiting disease in healthy adults and resolves within 7–10 days.
Predisposing factors for the development of acute bronchitis in children include poor nutrition, allergy, deficiencies in IgG2, IgG3, and IgG4 subclasses, and rickets.
Older patients who have emphysema or chronic respiratory disease (e.g., tuberculosis) are more likely to develop acute bronchitis.
Acute bronchitis usually follows a viral upper respiratory tract infection that extends into the trachea, bronchi, and bronchioles and results in a hacking cough and sputum production. The inflammation results in hypersecretion of mucus in the bronchial airways. The cough reflex aids in the elimination of mucous secretions from the airways. In time, bacteria can colonize the damaged airways causing the sputum to be purulent. If the patient is healthy, the viral infection is eliminated and the mucous membranes return to normal within 7–10 days. Mucociliary clearance of the airway may be delayed in patients who smoke or who are exposed to smoke because of excess mucous production and loss of ciliated cells, which leads to a productive cough. These patients are more likely to develop chronic bronchitis.
Diagnosis of acute bronchitis is based on clinical signs and symptoms. Differentiation between bronchitis and pneumonia is nearly impossible to determine based on clinical grounds unless chest radiographs demonstrate infiltrates or consolidation consistent with pneumonia. If the patient's temperature is elevated, a bacterial bronchitis may be present. Healthy persons usually improve with few complications.
Therapy and Prevention
Bronchitis in an otherwise healthy person is almost always self-limiting. Supportive therapy with analgesics (e.g., acetaminophen), antipyretics (e.g., ibuprofen), antitussives (e.g., dextromethorphan), and expectorants (e.g., guaifenesin) is recommended. If the patient has bronchitis of greater than 14 days, a fever, and if the sputum becomes purulent, it may be necessary to identify the bacterial pathogen by culturing the sputum and treating the patient with erythromycin or azithromycin.
There are no preventative measures available to treat all of the possible agents that can cause bronchitis. The influenza virus vaccine is available to prevent bronchitis due to this agent.
Bronchiolitis causes inflammation of the bronchial tree as low as the bronchioles but does not involve the alveoli. Because infants have narrower airways, bronchiolitis is usually a disease of infants younger than 1 year of age.
The most common cause of bronchiolitis is respiratory syncytial virus; other causes include human metapneumovirus, parainfluenza viruses, and adenoviruses.
Early symptoms of bronchiolitis are similar to symptoms of a viral upper respiratory tract infection and include mild rhinorrhea, cough, and sometimes a low-grade fever. In some infants and young children, the infection extends downward into the lower respiratory tract causing paroxysmal cough and dyspnea. Other common symptoms include tachypnea, tachycardia, fever (38.5–39°C), diffuse expiratory wheezing, inspiratory crackles, nasal flaring, intercostal retractions, grunting, vomiting (especially posttussive), cyanosis, and hyperinflation of the lungs and depression of the diaphragm.
The incidence of bronchiolitis parallels respiratory infections in older children and adults and is most common during fall and winter months.
Although infection with respiratory syncytial virus may occur at any age, the clinical disease bronchiolitis develops only in infants and young children. About 75% of cases of bronchiolitis occur in children younger than 1 year of age and 95% occur in children younger than 2 years of age, with a peak incidence at 2–8 months of age. The infection is usually self-limiting.
Bronchiolitis is an acute viral infection with a favorable outcome; fatalities rarely occur.
About 95% of children aged 2 have serologic evidence of past infection with respiratory syncytial virus; the presence of antibodies to this virus does not confer immunity.
Risk factors include: age younger than 6 months, bottle feeding, prematurity (born before 37 weeks' gestation), exposure to cigarette smoke, and crowded living conditions.
The virus is transmitted from person-to-person by direct contact with nasal secretions or by airborne droplets.
The risk of RSV lower respiratory tract infection (bronchiolitis) was 10 times higher for children who had older siblings, high parental educational levels, birth weights of >4 kg, attended day care, and were born between April and September, compared with children without these factors (M.L. Houben et al. Clinical Prediction Rule for RSV Bronchiolitis in Healthy Newborns: Prognostic Birth Cohort Study. 2011. Pediatrics. 127:35-41).
Bronchiolitis is usually a viral infection of the small airways (bronchioles). Infection of the bronchiolar respiratory and ciliated epithelial cells produces increased mucous secretion, cell death, and sloughing, followed by a peribronchiolar lymphocytic infiltrate and submucosal edema. Debris in the bronchioles and edema of the walls of the bronchioles results in critical narrowing and obstruction of these airways. Decreased ventilation of portions of the lung causes ventilation-perfusion mismatching resulting in hypoxia. The expiratory phase of respiration also causes dynamic narrowing of the airways resulting in decreased air flow from the lungs and air trapping. The patient must work harder to breathe, which is due to increased end-expiratory lung volume and decreased lung compliance. The debris present in the bronchioles is cleared by macrophages. The pulmonary epithelial cells regenerate within 3–4 days after the infection clears.
The diagnosis of bronchiolitis involves observation of the patient's signs and symptoms, chest radiographs, and antigen testing for respiratory syncytial virus in nasal washings. Chest radiographs should include anteroposterior (AP) and lateral views, which may show hyperinflation and patchy infiltrates, air trapping, focal atelectasis, flattened diaphragm, increased anteroposterior diameter and peribronchial cuffing.
Antigen tests of nasal washings provide rapid and accurate detection of respiratory syncytial virus. A positive culture or direct fluorescent antibody test result can confirm the diagnosis of respiratory syncytial virus bronchiolitis. Nasal washings should be obtained from children who are hospitalized and children at risk for severe disease.
Patients with bronchiolitis may require supplemental oxygen and replacement of electrolytes and fluids. Empiric treatment with beta agonists (e.g., albuterol) may be helpful in some cases. Anticholinergics (e.g., ipratropium) inhibit smooth muscle contraction and are useful in patients with severe bronchospasm. Studies on treatment of respiratory syncytial virus with ribavirin are mixed and several studies show no significant effect of this treatment on children with severe bronchiolitis. Currently if used it is recommended only in select patients with severe bronchiolitis.
To prevent bronchiolitis, RespiGam (immunoglobulin reactive with respiratory syncytial virus) or palivizumab (humanized monoclonal antibody reactive with respiratory syncytial virus) can be given to high-risk patients including infants born prematurely, patients with cystic fibrosis, patients who have hemodynamically significant acyanotic or cyanotic congenital heart disease, or patients who are immunodeficient.
To emphasize the importance of this disease, influenza is discussed as a separate topic. Although it is a self-limiting disease, severe complications leading to fatalities are seen in the very young, the elderly, patients with underlying cardiovascular and pulmonary diseases, and women in the third trimester of pregnancy.
The causative agent of influenza (or flu) is the influenza virus; the three different antigenic types of the virus are A, B, and C. Virus types A and B cause most epidemics and sporadic outbreaks of flu worldwide. Type C is usually seen as a mild disease of the very young, and rarely causes a flu epidemic. By age 15, nearly everyone has developed antibodies to the type C virus.
A distinctive terminology is used when discussing influenza A virus— the type of influenza virus, the geographic location where it was first isolated, the month it was first isolated, the year it was first isolated, and the H and N antigens expressed (e.g., A/Ann Arbor/1/86/H1N2—an influenza virus type A, first isolated in Ann Arbor, Michigan, in January of 1986 that is a H1N2 type). Influenza B viruses are identified by type, place first isolated, and the date first isolated but NOT by the H and N types.
Symptoms of influenza include abrupt onset of fever (38.9–40°C), chills, rigors, headache, congested conjunctiva, extreme prostration with myalgia in the back and limbs, nonproductive cough, and injection of the pharynx and conjunctiva. Diarrhea and vomiting can also be present but are usually only seen in children with influenza. Fever usually abates within 3–4 days, and recovery usually is complete within 1 week. Cough and malaise may persist for 2 weeks or longer.
In very young, the elderly, patients with underlying cardiovascular and pulmonary diseases, and women in the third trimester of pregnancy, the condition may worsen with persistent fever, marked prostration, cough with rales, and pneumonia. The pneumonia usually is due to a secondary bacterial infection, which can include Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, or Streptococcus pyogenes.
Adults are infectious from 1 day before symptoms begin through approximately 5 days after onset of illness. Severely immunocompromised persons can shed the virus for weeks to months.
Rates of influenza infection are highest among children, but rates of serious illness and death are highest among persons aged 65 or older and persons of any age who have medical conditions that place them at high risk for complications from influenza (e.g., pulmonary or cardiac disease).
Epidemics of influenza usually occur every year during the winter months and are responsible for an average of approximately 36,000 deaths per year in the US.
Epidemic flu is cyclic and is usually caused by virus types A or B. Epidemics of type A occur every 2–3 years. Epidemics of type B occur every 4–6 years. Epidemics usually occur from late autumn to early spring.
The most common complications associated with influenza infection are pneumonia and death. The overall mortality rate is about 1%. Influenza can exacerbate underlying medical conditions and lead to secondary bacterial pneumonia or primary influenza viral pneumonia.
Young children with influenza infection can develop symptoms mimicking bacterial sepsis and have high fevers. Some children hospitalized with influenza may have febrile seizures.
Influenza viruses are spread from person to person primarily by the coughing and sneezing of infected persons. Another way to describe it is as follows: the virus is spread through close contact, which is defined as within six feet of an infected person.
Avian influenza is caused by influenza A virus H5N1 that primarily infects birds.
Outbreaks of H5N1 among poultry have occurred in Africa, East Asia, and the Pacific, South Asia, the Near East, Eurasia, and Europe.
The mortality rate is high, at around 60%. Most patients acquired the infection after direct close contact with infected poultry or contaminated surfaces.
A few rare cases of human-to-human spread of H5N1 virus have occurred, although transmission did not continue beyond one person.
Another avian virus has made the news; Influenza A- H7N9 (southeastern China 132 cases; 37 fatalities)
The influenza viruses are segmented single-strand RNA viruses. Influenza types A and B viruses have eight RNA segments, and influenza type C virus has seven RNA segments. The RNA codes for five structural proteins and three nonstructural proteins. Protein M and nucleoprotein NP are used to place the virus into types A, B, and C. The hemagglutinins (H antigen) and the neuraminidases (N antigen) are important in the pathogenesis of influenza—the H antigen is required for binding of the virus to the cell, and the N antigen helps the mature virus escape from the cell.
In addition to the major types of the influenza A virus, there are also subtypes of the virus that are determined by the H and N antigens. There are at least five antigenic types of H antigen (i.e., H1, H2, H3, H5, and H7) and three antigenic types of N antigen (N1, N2, and N9) that infect humans. Antibodies to one type of H or N antigen are not effective in protecting a person from being infected by another type of the H or N antigen.
Influenza viruses can infect other animal hosts (e.g., ducks, swine). Two different influenza A viruses can infect the same animal host cell, and as long as the viruses that result from this dual infection have the right number and kinds of RNA segments, they can cause infection in another host.
If two viruses are circulating in a population of swine (e.g., influenza A H5N2 virus and influenza A H1N1), the viruses can co-infect one animal. Suppose, for example, that one of these two viruses, the influenza A H1N1 virus, infected several persons the previous year. Because of their ability to produce antibodies that inactivate the influenza A H1N1 virus, those who survived the influenza A H1N1 infection would not acquire this viral infection again the following year. However, if influenza A H1N1 virus and influenza A H5N2 virus co-infected a pig and re-assorted their viral RNA segments, an influenza A H5N1 virus could result. The influenza H5N1 virus could cause the next influenza epidemic in humans if they were exposed to the infected pig with the re-assorted virus. These major changes in H or N types are called shifts. The H5N1 Influenza A virus in this example represents an antigenic shift.
Mutations can also occur in the H and N genes that result in slight changes in the H or N antigens. These slight changes are called antigenic drift. Influenza A viruses undergo both shift and drift, whereas influenza B viruses only undergo drift in their H and N antigens.
If a susceptible person inhales droplets containing the influenza virus, the virus attaches to the epithelial cells lining the respiratory airways as well as to the nasal turbinates. The virus replicates in the cells, causing desquamation of ciliated epithelium, hyperplasia of transitorial cells, edema, hyperemia, congestion, and increased secretions. Pneumonic complications without secondary bacterial infections can occur; however, they usually are due to a secondary infection with bacteria (commonly Staphylococcus aureus).
Diagnosis of influenza is difficult in that there are no pathognomonic signs and the infection can be easily confused with other respiratory tract infections. Influenza can be differentiated from the common cold because the flu results in a high fever but the common cold is an afebrile disease. Differentiating influenza pneumonia from atypical pneumonia may be difficult however; the onset of atypical pneumonia is usually insidious whereas influenza is rapid in onset.
Definitive diagnosis requires laboratory testing. There are several tests available and include direct antigen detection tests, virus isolation in cell culture, or detection of influenza-specific RNA by real-time reverse transcriptase-polymerase chain reaction (rRT-PCR). Rapid influenza diagnostic tests (RIDTs) are available and they detect the viral nucleoprotein antigen.
RIDTs can detect viral antigen in patient samples within 30 minutes or less and are referred to as "point-of-care" tests since CLIA-waived (Clinical Laboratory Improvement Amendments) the requirement that skilled medical technicians need to perform these tests. RIDTs can i) detect and distinguish between influenza A and B viruses; ii) detect both influenza A and B but not distinguish between influenza A and B viruses; or, iii) detect only influenza A viruses. RIDTs have low to moderate sensitivity compared to viral culture or RT-PCR. The sensitivities of RIDTs to detect influenza B viruses are lower than for detection of influenza A viruses. Sensitivities of RIDTs are higher in samples taken from children than in samples taken from adults.
In uncomplicated cases of influenza, recovery is usually complete, with no residual effects. Supportive care is recommended for patients with healthy immune systems. Antipyretics and analgesics can provide relief for fever and muscle pain. The antiviral drugs described below are only effective in reducing illness severity and shortening duration of illness if given within the first two days of influenza symptoms.
Antiviral drugs for influenza are an adjunct to influenza vaccine for controlling and preventing influenza. Four licensed influenza antiviral agents are available in the U.S.: amantadine, rimantadine, zanamivir, and oseltamivir. Amantadine and rimantadine are effective against influenza A viruses but NOT against influenza B viruses. Amantadine and rimantadine can be used in chemoprophylaxis and in the treatment of influenza A viral infections in adults. Only amantadine can be used in the treatment of influenza A viral infections and chemoprophylaxis in children aged 1 year or older. Rimantadine can only be used for chemoprophylaxis in children.
Zanamivir and oseltamivir are chemically related antiviral drugs known as neuraminidase inhibitors that have activity against both influenza A and B viruses. Both drugs are approved for treating uncomplicated influenza infections. Zanamivir is approved for treating persons aged 7 years or older and for chemoprophylaxis of influenza among persons aged 5 years or older. Oseltamivir is approved for treatment and for chemoprophylaxis of influenza among persons aged 1 years or older. Oseltamivir resistance was widespread in the influenza A H1N1 strains during the 2008/2009 flu epidemic. Treatment with zanamivir or a combination of oseltamivir and rimantadine or amantadine is now recommended in situations where the influenza subtype is likely to be H1 or unknown.
The seasonal influenza vaccination contains three different influenza viruses (two As and one B). Vaccination and chemoprophylaxis with amantadine, rimantadine, or oseltamivir are useful for the prevention of seasonal influenza disease in high-risk groups. Use of antiviral medications for postexposure chemoprophylaxis should be reserved for persons at higher risk for influenza-related complications who have had contact with someone likely to have been infected with influenza. An emphasis on early treatment once a patient has developed symptoms, rather than chemoprophylaxis, should reduce opportunities for development of oseltamivir resistance. Chemoprophylaxis should not be used for prevention of illness among healthy persons after exposures in community settings.
Vaccination campaigns begin in mid-August and end in mid-November. Vaccination is recommended for all persons over 6 months of age. In 2013-2014 all vaccines will contain the following: A/California/7/2009pdm09-like (2009 H1N1), an A/Victoria/361/2011 (A/Texas/50/2012), and a B/Massachusetts/2/2012-like (B/Yamagata lineage) virus.
Pertussis (also known as whooping cough) was once a rare disease but is now becoming more common in the US. The word pertussis means cough, and the pathognomonic whoop following a paroxysmal coughing episode aids greatly in diagnosis. In the US., Bordetella pertussis causes about 95% of cases of pertussis, and Bordetella parapertussis causes the other 5% of cases.
Bordetella pertussis is a gram-negative cocco-bacillus.
Pertussis is a coughing illness that lasts at least 2 weeks and has one of the following manifestations: paroxysms of coughing, inspiratory "whoop," or posttussis vomiting without any other apparent cause. The incubation period for pertussis is 7–10 days, which is followed by the catarrhal phase. During the catarrhal phase, the disease is indistinguishable from an upper respiratory tract infection. The person is most infectious during this phase, which is characterized by the insidious onset of coryza, sneezing, low-grade fever, and a mild occasional cough similar to the cough of the common cold. The cough gradually becomes more severe and after 1–2 weeks, the second, or paroxysmal, stage begins.
The paroxysmal phase begins with episodic, sudden coughing and generally lasts 2–4 weeks. The cough is so severe that patients are unable to sleep or eat. The whoop, if present, results from inspiratory stridor and is pathognomonic. The patient has paroxysms of numerous, rapid coughs. When paroxysm ends, a long inspiratory effort is usually accompanied by a pathognomonic high-pitched whoop. During such an attack, the patient may become cyanotic. Vomiting and exhaustion commonly follow the episode. The patient usually appears normal between attacks. Paroxysmal coughing attacks occur more frequently at night, with an average of 15 attacks per 24 hours. Severe cases result in hemoptysis, subconjunctival hemorrhages, hernias, seizures, and death.
Adults with pertussis infection may complain of chronic cough. They may be asymptomatic or they may present with an illness that ranges from a mild cough to classic pertussis, with persistent cough lasting more than 7 days. Inspiratory whoop is uncommon.
B pertussis is inhaled on respiratory droplets and attaches to the ciliated epithelium in the trachea. The pertussis toxin causes almost all of the tissue damage in the trachea. The pertussis toxin is an enzyme that ribosylates guanine–nucleotide-binding protein with adenosine diphosphate, affecting regulatory mechanisms in the ciliated cells that line the host's trachea. This causes death and sloughing of the ciliated cells. Other products of importance are the tracheal cytotoxin and a filamentous hemagglutinin. The cytotoxin kills the cells that line the trachea, and the filamentous hemagglutinin is important in the attachment of B pertussis to the ciliated cells. Large amounts of mucus are produced in response to the infection and cause the patient to cough. The neurologic effects of infection are associated with hypoxia, lymphocyte plugging, and intracerebral hemorrhage.
Pertussis occurs worldwide and results in one million deaths a year, with most of the deaths occurring in underdeveloped countries.
The number of pertussis cases rapidly increased from 2001 to 2004 (incidence of 2.69 to 8.8 per 100,000). In 2007 the numbers of cases rapidly decreased but are still significantly higher than what was reported in the 1990's. In 2011 there were 18,719 cases reported to the CDC.
Adolescents and adults account for most reported cases.
Older patients have better outcomes than younger patients.
Up to 50% of cases of children with pertussis can be traced to adults with a chronic cough. A carrier state does not exist; however, persons in close contact with symptomatic patients may transiently harbor the organism.
Adolescents and adults are critical age groups as they are believed to be the main source of transmission of pertussis to young infants who are too young to be completely vaccinated.
In 2005, a combined tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) was recommended for use among adolescents and adults to boost their immunity and prevent spread from adolescents and adults to susceptible infants.
The most severe cases of pertussis are in children younger than 12 months of age. Prognosis is dependent on the age of the patient, the state of health, and availability of supportive care.
The risk of nonfatal neurologic damage due to infection is at least 6–10 times greater than the risk associated with immunization against pertussis.
The disease is highly infectious. Infection does not ensure protection from a second infection with B pertussis.
Humans are the only natural hosts; the disease is transmitted person to person via aerosolized droplets.
The presence of the whoop is pathognomonic for pertussis. Laboratory procedures necessary for diagnosis include nasopharyngeal aspirates plated on Bordet-Gengou medium, immunofluorescent staining of nasal secretions for B pertussis, and serologic testing (ELISA) with acute and convalescent sera. An elevated white blood cell count with a lymphocytosis is usually present in children, which is unusual for a bacterial infection. Most bacterial infections result in an increase in neutrophils rather than an increase in lymphocytes.
Antibiotics are ineffective in shortening the course of pertussis infection once the patient has entered the paroxysmal stage. If antibiotics are given, erythromycin is the drug of choice and will eradicate the organism from secretions and decrease spread of the infection to others and, if initiated early, may modify the course of the illness.
Supportive care is essential in the prevention of hypoxia and pulmonary complications. An antibiotic effective against pertussis (e.g., azithromycin, erythromycin, or trimethoprim-sulfamethoxazole) should be administered to all close contacts of persons with pertussis, regardless of age and vaccination status.
The best means of preventing pertussis is vaccination. The most commonly used vaccine is the acellular pertussis vaccine (DTaP), which is mixed with diphtheria and tetanus toxoids and is given to children aged 6 weeks to 6 years. Herd immunity does not seem to completely protect unvaccinated children from pertussis (Glanz JM, McClure DL, Magid DJ, et. al. 2009. Parental Refusal of Pertussis Vaccination is Associated with Increased Risk of Pertussis infection in Children. Pediatrics 123(6):1446-51). One in 20 children whose parents do not get them vaccinated against pertussis will get this disease whereas only 1 in 500 children who were vaccinated developed pertussis.
Because of the waning immunity of adolescents and adults to pertussis and asymptomatic infections that spread from asymptomatic adolescents and adults to unprotected infants, vaccine recommendations have been expanded to give persons older than 10 years of age the tetanus-diphtheria-acellular pertussis vaccine rather than the tetanus-diphtheria vaccine for their scheduled booster shot. Vaccine coverage rates in adolescents and adults are currently around 41% (2008 data).
Revised 8/21/14


German Ambassador to Pakistan Martin Kobler expressed his disappointment on Friday with Shireen Mazari's statement regarding the European Union's (EU) approach towards refugees.
The envoy retorted clarifying that Germany had taken in one million Syrian refugees in 2015 under directives by chancellor Angela Merkel.
"disappointed by this statement: i think its not fair. chancellor merkel took courageous decision in 2015 to receive around 1 mio refugees in #germany who fled syria. #germany hosts today 1,4 mio refugees. last week german government accepted many refugees crossing mediterrean," he tweeted.


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Slovo Ponor se užívá ve více významech

 ponor (speleologie) – místo, kde se vodní tok propadá z pozemního koryta do podzemí, nejčastěji v krasu
 ponor (loď) – vzdálenost dna lodi od hladiny
 ponor (potápění) – činnost potápěče od sestupu pod hladinu do výstupu na povrch
 Ponor (Alba) – osada v rumunském okrese Alba
 Ponor (Chorvatsko) – vesnice v chorvatské opčině Cetingrad v Karlovacké župě
 Ponor (Hunedoara) – vesnice v rumunském okrese Hunedoara
 ponor (rod) (Oreocallis) – rod rostlin z čeledi proteovité

Související články
 ponorka

Externí odkazy

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If you haven't checked out our Basic SmartVideo tag options article, you should do so, as >95% of use cases are are addressed by the options shared on that page. However, if you're an advanced user with a unique configuration need that is not met in that article, keep reading!
You might have noticed that controls is included in every SmartVideo tag. That's because, in the majority of cases, controls are desired so that a user is able to alter playback. To remove controls from the player, simply remove controls from the tag.
Pro tip: if you remove controls, make sure to set the video to autoplay (and muted to make sure autoplay works). If you don't, the user will have no way of beginning video playback.
Safari on iOS forces videos to go fullscreen. Use playsinline to tell Safari not to.
Removing class="swarm-fluid" tells the player to maintain height and width no matter what changes are made to the size of the browser window. We haven't found a great use for this option yet, but if you find one, let us know!
That's it for our advanced SmartVideo tag options!
If you need even more advanced options, just reach out and we'll tell you what's possible!


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redpajama_set_name: RedPajamaGithub


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Development of novel optical imaging techniques for fundamental and clinical applications including photoacoustic microscopy, photoacoustic computed tomography, optical coherence tomography, diffuse optical tomography and fluorescence molecular tomography.
1. Qian Chen, Heng Guo, Tian Jin, Weizhi Qi, Huikai Xie, Lei Xi* "Ultracompact high-resolution photoacoustic microscopy" Optics Letters, Accepted, 2018.
2. Wei Qin,# Tian Jin,# Heng Guo, Lei Xi* "Large-field-of-view optical resolution photoacoustic microscopy" Optics Express, 26, 4271-4278, 2018.
3. Heng Guo, Chaolong Song, Huikai Xie and Lei Xi* "Photoacoustic endomicroscopy (PAEM) based on a MEMS scanning mirror" Optics Letters, 42, 4615-4618, 2017.
4. Tian Jin, Heng Guo, Huabei Jiang, Bowen Ke and Lei Xi* "Portable optical resolution photoacoustic microscopy (pORPAM) for human oral imaging " Optics Letters, 42, 4434-4437, 2017.
5. Lei Xi*, Tian Jin, Junli Zhou, Paul Carney, Huabei Jiang "Hybrid photoacoustic and electrophysiological recording of neurovascular communications in freely-moving rats" Neuroimage, 161, 232-240, 2017.
6. Lei Xi*, Huabei Jiang"High resolution three-dimensional photoacoustic imaging of human fingerjoints in vivo" Applied Physics Letters, 107(6), 063701, 2015.
7. Lei Xi, Chaolong Song and Huabei Jiang "Confocal photoacoustic microscopy using a single multifunctional lens," Optics Letters, 39(11), 3328-3331, 2014.
8. Lei Xi, Minati Satpathy, Qing Zhao, Weiping Qian, Lily Yang, Huabei Jiang"HER-2/Neu targeted delivery of a nanoprobe enables dual photoacoustic and fluorescence tomography of ovarian cancer," Nanomedicine: Nanotechnology,Biology and Medicine, 10(3), 669-677, 2014.
9. Lei Xi, Stephen Grobmyer, Guangyin Zhou, Weiping Qian, Lily Yang, Huabei Jiang"Molecular photoacoustic tomography of breast cancer using receptortargeted magnetic iron oxide as contrast agents," Journal of Biophotonics, 7(6), 401-409, 2014.
10. Lei Xi, Stephen R. Grobmyer, Lei Wu, Ruimin Chen, Guangyin Zhou,Luke G. Gutwein, Jingjing Sun, Wenjun Liao, Qifa Zhou, Huikai Xie, and Huabei Jiang "Evaluation of breast tumor margins in vivo with intraoperative photoacoustic imaging," Optics Express, 20(8), 8726-8731, 2012.
11. Lei Xi, Xiaoqi Li, Huabei Jiang "Design and evaluation of a hybrid photoacoustic tomography and diffuse optical tomography system for breast cancerdetection," Medical Physics, 39(5), 2584, 2012.


As a student, all of my PHP projects were "handmade", starting from scratch. After several projects, I realized that I wasted much time setting up basical things, or resolving recurrent problems. That's when the framework comes in.
My bachelor's work placement provided me with the opportunity to discover Symfony2, my first PHP framework. In short, I would have needed between 4 and 5 months to do what I've done in 2 months with this tool. In the end of this placement I decided to pay more attention about frameworks.


I sat hungrily in services this past weekend during Yom Kippur – along with hundreds of other people who were thinking about nothing but the bagels and whitefish that were waiting on the other side of the next 26 hours. It's hard to concentrate when you are starving, having coffee withdrawal ( me!) and freezing your tush off on the metal folding chairs that must be stored in the refrigerator when they are not being used. I got bored staring at the strange woman in front of me and tried very hard not to gossip or be catty whilst repenting for my sins of the past year.
There were a few bright spots however… aside from the moment when no one was looking and I snuck a piece of gum into my mouth. The challenge of trying to chew my gum without moving my mouth brought me right back to all that contraband gum chewing when I was a child. The funny thing is that I actually thought that no one could see me because I was doing it so slowly… next week I might try covering my eyes to see if everyone really does disappear just because I can't see them!
Before I discuss the sermon, I somehow have to reconcile what my life looks like on the outside to what it feels like on the inside. While this might sound a little bit like a commercial for an Oreo, it makes perfect sense to me. How it looks is completely different from how it feels. I often feel like a mess. I feel like my clothes are wrong, my hair needs to be cut, my house is too small, too cluttered, too messy. My kids are whiny and tired and hungry. Our food is too fattening, our family is odd, our bank account is overdrawn, our bills are late, our winter clothes are too bulky, our laundry is never done, the refrigerator never has what anyone wants, the grass is too long, the flowers always die and the car is a trash can on wheels. These things make me feel like I haven't succeeded at anything. They seems like a constant reminder of all that isn't right.
However; on the outside, what the world can see is that my children are beautiful, healthy, and clean. My house is cute and charming and warm. Our food is delicious and plentiful and sweet. My clothes are stylish and funky and (usually clean.) My hair is short and easy. My husband is kind and loving, funny and silly and tall! My friends are smart and interesting and generous. Our family is whole and good and safe.
Why do these two pictures seems so contradictory? In any event, for once,everything seemed aligned…at about 8 p.m. on Sunday night. Despite all the shortcomings, I am very proud of our accomplishments this past year. We completely a documentary about Max, titled, "Saying Yes." It was about how Max was fully and completely included in our local nursery school despite having CP and being the only child to ever go there in a wheelchair. It was about all the times that good, open-minded people said "yes," instead of no. I never made a film before. It was so low budget that I edited most of it myself. I don't know anything about editing. But, I know a lot about Max and about what makes people feel good. It came out perfectly. The story was so wonderful that people came from all over to see it. Old friends and family from far away, professionals with whom we worked to adopt the kids, therapists and doctors. Friends whom I haven't seen in 20 years sent contributions toward the cost. Publicity for it was in the newspaper, online and all over town.
As a result of the short film, our synagogue was given a lot of good press . The right people were applauded for once and the kindness of our community was highlighted. The story traveled all over the country; and because of it, children in Arizona, Florida and Colorado will have a chance to be included in ways never thought possible. Just this week, a movie producer for ABC worked with me to include the story in a movie that will air in December.
This was because of us, our family and our desire to make having a child with a disability something more than a tragedy. We wanted to celebrate something. We wanted to show that there are people who do the right thing and because of that, the entire world can be changed. Things don't have to stay the way they are. They can improve. This is what the Rabbi spoke about. I have never been more proud of my family in my entire life.


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Hemisolinus helenae es una especie de arácnido del orden Pseudoscorpionida de la familia Olpiidae.

Distribución geográfica
Se encuentra en la Isla Santa Elena.

Referencias

Olpiidae
Arácnidos de África


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Biden's Executive Order: Taking Aim at Non-Competes
Jul 13, 2021 | Employment Law
On Friday, July 9, 2021, President Biden signed a sweeping executive order covering a broad range of activities which may impact competition in the marketplace. The President's directives in the executive order range across several different industries and involve multiple federal agencies, including the Department of Health and Human Services (HHS), the Federal Trade Commission (FTC), and the Securities and Exchange Commission (SEC). President Biden's instructions and comments on non-compete covenants may be of particular interest to businesses in the healthcare industry.
As healthcare providers are well aware (and as attorneys at Chilivis Grubman previously discussed here), non-compete agreements are a contentious and key negotiation point in many healthcare transactions, and especially in physician employment agreements. The removal of non-compete covenants from the healthcare industry would have serious implications.
In Section 5(g) of the executive order, President Biden speaks directly to the FTC:
To address agreements that may unduly limit workers' ability to change jobs, the Chair of the FTC is encouraged to consider working with the rest of the Commission to exercise the FTC's statutory rulemaking authority under the Federal Trade Commission Act to curtail the unfair use of non-compete clauses and other clauses or agreements that may unfairly limit worker mobility.
Expect Roadblocks and Limitations
Despite the President's executive order and campaign rhetoric on non-compete covenants, there's no way to know how far the FTC can and will take this directive until the FTC releases a proposed rule. Additionally, the FTC can expect to face some significant legal challenges, including: (1) whether the FTC has authority under the Federal Trade Commission Act to establish criteria for determining permissible contractual restraints on employees, and (2) whether a federal agency can step into an area of law that has, to date, been governed by state law.
Considering the executive order, here are a few key points on non-competes to consider, for now:
The executive order does not invalidate current non-compete covenants.
The rulemaking process for federal agencies is a lengthy process and with the anticipated legal challenges, it may be a long time before we see a final, enforceable rule.
A final rule from the FTC may ultimately be limited to specific subsets of "non-essential" employees, or to employment in certain industries.
The executive order's language appears to apply to non-compete covenants between employees and employers specifically and is silent on non-compete covenants in other scenarios, such as a covenant tied to the sale of a business.
The attorneys at Chilivis Grubman have extensive experience with drafting and negotiating physician non-compete covenants, both in the context of employment agreements and the sale of a business. If you need assistance with such a matter, please contact us today.

redpajama_set_name: RedPajamaCommonCrawl


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Sanchez: I was impatient
Upgrading your space while stuck at home? Get it insured
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Carla Fried: How keeping a car 15 years can pay you $230,000
Tesla: record sales, but missing target
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Oct. 9, 2010 Updated: Oct. 9, 2010 12:25 a.m.
Rick Sanchez didn't mince any words. He said he was wrong and he screwed up.
Interviewed on ABC's "Good Morning America" a week after being fired from his hosting job at CNN, Sanchez apologized Friday for his slams at CNN and at Comedy Central's Jon Stewart, whom he had called a "bigot."
Those remarks were aired on a radio program on Sept. 30.
Sanchez explained that he was tired when he made the radio appearance, and that "my daughter had a softball game I desperately wanted to go to, and I was a little impatient. I said some things I shouldn't have said. They were wrong. Not only were they wrong, they were offensive."
A day later, he was out of a job.
He has no beef with Stewart or with CNN, he insisted, although, when pressed by "GMA" anchor George Stephanopoulos, Sanchez seemed to still be chafing from ill treatment.
"Is that really fair? Why is it always me?" he said, trying to account for his response on past occasions when Stewart singled him out for lampooning on "The Daily Show," a satiric newscast.
He also referred to the "landscape" of cable-news prime-time hosts: "There's not a single Hispanic, a single Asian-American, or a single African-American," he said.
"I'm not trying to make excuses," Sanchez summed up.
Tina Fey set for a special 'SNL' women's reunion
NBC says that "30 Rock" star Tina Fey is paying a return visit to "Saturday Night Live" for a prime-time special showcasing some of its funniest ladies.
Along with vintage clips, the special will include original material featuring Fey and other "SNL" alumnae including Ana Gasteyer, Julia Louis-Dreyfus, Laraine Newman, and "Parks and Recreation" star Amy Poehler, along with current cast member Kristen Wiig.
Titled "The Women of 'SNL,'" the two-hour special is scheduled to air on NBC on Nov. 1.
Kathryn Erbe returns to 'Law & Order: CI'
USA Network says Kathryn Erbe is coming back to "Law & Order: Criminal Intent" for the drama's 10th and final season.
Erbe will be reunited with Vincent D'Onofrio, who's also returning to the crime drama for its last year.
Series creator Dick Wolf said Friday that he's grateful Erbe agreed to rejoin what Wolf called one of TV's best detective teams.
Eight new episodes of "Law & Order: Criminal Intent" starring Erbe as New York police Detective Eames and D'Onofrio as Detective Goren will air starting in 2011. The debut date was not announced.
Al Pacino to star in film as producer Phil Spector
HBO says Al Pacino is set to star as legendary record producer Phil Spector in a TV film to be written and directed by David Mamet.
The film will tell the story of Spector, who long ago recorded such acts as the Beatles, Cher and the Ramones. Now, at age 70, he's serving a prison sentence of 19 years to life for murder. He was convicted for the 2003 shooting death of actress Lana Clarkson.
The 70-year-old Pacino starred in the HBO film "You Don't Know Jack" earlier this year as Jack Kevorkian, who served time in prison for assisting in the suicide of a terminally ill man.
Rock Hall dedicates Lennon time capsule
On the eve of his 70th birthday, the Rock and Roll Hall of Fame and Museum in Cleveland has dedicated a time capsule in honor of John Lennon containing several CDs, DVDs and books and two notes written by widow Yoko Ono.
The stainless steel capsule dedicated Friday will be kept in the Cleveland museum's archives at a nearby college campus.
Assistant curator Meredith Rutledge tells The Plain Dealer that the goal of the capsule was to preserve the "legacy of peace and love" of the former Beatles member.
About 100 people attended the dedication, which marks the start of a weekend of events in honor of Lennon's birthday. The capsule is scheduled to be opened in 2040, on Lennon's 100th birthday.
Lennon was killed in 1980 outside the New York City apartment building where he lived.
Ballerina fired after posing for nude photos
The management of the Vienna State Opera and its ballet company says it has fired a ballerina for posing in the nude after she was warned not to do it again.
The management of the prestigious institutions says solo dancer Karina Sarkissova was axed Aug. 23 after a series of provocative photos of her appeared in the September issue of the Austrian men's fashion and lifestyle magazine "Wiener."
A statement Friday said she had already been reprimanded in May for nude shots that were taken in the opera house without permission and published in the June edition of "Penthouse."


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Android iPhone and iPad
The 5 Best Meditation Apps for Relaxing and Sleeping
James Frew April 25, 2019 25-04-2019 5 minutes
Mindfulness and meditation have become mainstream over the past few years. One of meditation's key benefits is that regular practice can help make you feel more relaxed. This is especially important for when you want to get your head on the pillow and drift off to sleep.
You'll find several meditation apps that focus on helping you relax, and when the time comes, fall asleep. Here are the best meditation apps for relaxing and sleeping.
1. Headspace
Headspace is one of the most popular meditation apps and is widely credited for making app-based meditation a part of modern life. The app was co-created by Richard Pierson and Andy Puddicombe, a former Buddhist monk.
There are 10 free meditations for you to use; anything more requires a subscription. However, with that subscription, you get access to Headspace's entire library of meditations. These are broken down into themes like happiness, relaxation, and sleep. The app gamifies meditation, increasing your Run Streak for each consecutive day you meditate with Headspace.
The app has introduced an entire section dedicated to sleep. This new feature has meditations to help you unwind before bed, along with ambient music and some audio visualizations called Sleepcasts. If you have difficulty sticking to a regular bedtime, you can ask Headspace for a gentle nudge when it's time to wind down.
Download: Headspace for Android | iOS (Free trial, subscription required)
2. Calm
Calm is another service offering app-based meditations. However, while Headspace's primary focus is meditation, Calm aims at a range of mindfulness and wellbeing techniques.
It was among the first of its kind to add a dedicated section devoted to sleep, known as Sleep Stories. These are stories read by celebrities noted for their pleasing voices like Stephen Fry and ASMR artist Emma Whispers Red, alongside archival recordings of Bob Ross.
Sleep Stories are updated weekly, so there should always be something new when you load up the app. If you experience ASMR, you might also want to watch some YouTube videos that'll trigger ASMR What Is ASMR? 10 YouTube Videos That Will Give You Shivers What Is ASMR? 10 YouTube Videos That Will Give You Shivers ASMR is defined as a pleasurable feeling triggered by certain kinds of unique stimuli. Use these YouTube videos to see if you have ASMR! Read More .
Calm offers a limited number of meditations for free, but if you want access to the whole library, you'll need to join Calm Premium. As part of the premium subscription, you can view Calm Body, a series of instructional videos that guide you through mindful movement—a mix between meditation and yogic stretching.
Download: Calm for Android | iOS (Free trial, subscription required)
3. Insight Timer
Insight Timer is one of the most successful free meditation apps for Android and iOS. Unlike many similar apps, Insight Timer makes its library of 15,000 guided meditations available for free. If you prefer unguided meditations, the app's Timer allows you to customize your session by length and ambient noise, along with bell type and frequency. This is important, as controlling the noise around you helps you stay focused How to Stay Focused by Controlling the Noise Around You How to Stay Focused by Controlling the Noise Around You Do you have trouble staying focused? Learn about how to use noise colors to improve your focus and productivity. Read More .
While most of the content is free, Insight Timer also offers a premium subscription. This grants you access to a new meditation each day, 10 and 30-day meditation courses, and offline playback. If getting a good night's sleep is high on your priority list, you may want to invest in the premium subscription solely for access to the app's Night mode.
The 914 dedicated sleep meditations come from over 500 teachers, so you should be able to find a session that works for you. If you join Insight Premium, there is even a 10-day course on getting deeper sleep.
Download: Insight Timer for Android | iOS (Free, subscription available)
4. Sleepfulness
Most mindfulness apps primarily focus on meditation, with sleep as a secondary focus. However, Sleepfulness, as the name suggests, is entirely dedicated to helping you get a better night's sleep. The app was developed by Mindfulness Everywhere, which also released the meditation app Buddhify.
If you've ever used Buddify, you'll know that the experience is different from many other meditation apps. You can select sessions by scrolling through a play wheel that groups them into four categories; Going to Bed, Can't Sleep, Waking Up, or Daytime. You can opt to have some appropriate music play for up to 10 minutes at the end of each session too.
Sleepfulness also customizes your experience through in-app questionnaires. The answers you give to these questions feed into the app's Insights section. This offers you session recommendations, along with guidance and facts to improve your time with Sleepfulness and get a better night's rest.
Download: Sleepfulness for Android | iOS (Free, in-app purchases available)
5. Stop, Breathe & Think
Stop, Breathe & Think (SBT) started life as part of the non-profit organization Tools for Peace. It aims to teach mindfulness and meditation to teenagers; the development of SBT emerged from that work. It was initially intended for those under 25, but has since grown into a mindfulness app suitable for all ages.
The goal of Tools for Peace and SBT is to help develop kindness and compassion in everyday life. To that end, the meditations broadly revolve around how finding inner peace can cultivate kindness towards others. The emphasis is on building a habit, so the default meditation is just five minutes long. This is manageable enough to fit into even the busiest days.
The app offers over 40 free meditations, and an additional 100 unlock with a premium subscription. SBT caters to those who want to improve their sleep too. There are sleep-specific meditations, soundscapes, and breathing exercises to help you get some shuteye.
Download: Stop, Breathe & Think for Android | iOS (Free, subscription available)
The Best Meditation App for You
In our increasingly busy world, it's essential to make time for yourself to relax and get some good quality sleep. Just a few minutes using one of these guided meditations apps should help you on your way to a more content state of mind. You might still be concerned by the quality of your slumber though. Fortunately, there are apps for tracking your sleep that may be able to help.
If you feel you've been spending too much time on your phone, it may help to be mindful of how you use it. In that case, you should consider installing an app that'll help you fight your smartphone addiction The 5 Best Apps to Help You Fight Your Smartphone Addiction The 5 Best Apps to Help You Fight Your Smartphone Addiction Are you addicted to your smartphone? These mobile apps will help you salvage your personal life and regain your productivity. Read More too.
Explore more about: Android Apps, Health, iOS Apps, Mental Health, Relaxation, Sleep Health.
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I use Strive Minutes which is a timer and doesn't have guided meditations and is quite minimal. But i needed that as i found myself fiddling with the options and settings a lot in some of the other apps.
James Frew
The best app is the one you actually use. If the other options were more than you needed, then it's great you found a timer which is right.
Insight timer is the best. So much content and no subscription needed
It's a good option for sure!
Bhagyasri
I'm doing sahaja yoga .. it's best compared to all..
I'm glad that works for you. Is there an app you use?
James Frew 164 articles
James is MakeUseOf's Buying Guides Editor and freelance writer passionate about making technology accessible and safe for everyone. Alongside technology writing, also interested in health, travel, music, and mental health. BEng in Mechanical Engineering from the University of Surrey. Can also be found writing about chronic illness at PoTS Jots.
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