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1.  Neuropsychological Measures of Attention and Impulse Control among 8-Year-Old Children Exposed Prenatally to Organochlorines 
Environmental Health Perspectives  2012;120(6):904-909.
Background: We previously reported associations between organochlorines and behaviors related to attention deficit hyperactivity disorder among boys and girls at 8 years of age using a teacher’s rating scale for a birth cohort in New Bedford, Massachusetts (USA).
Objectives: Our goal was to corroborate these findings using neuropsychological measures of inattentive and impulsive behaviors.
Methods: We investigated the association between cord serum polychlorinated biphenyls (PCBs) and p,p´-dichlorodiphenyl dichloroethylene (p,p´-DDE) and attention and impulse control using a Continuous Performance Test (CPT) and components of the Wechsler Intelligence Scale for Children, 3rd edition (WISC-III). Participants came from a prospective cohort of children born during 1993–1998 to mothers residing near a PCB-contaminated harbor in New Bedford. Median (range) cord serum levels for the sum of four prevalent PCBs [congeners 118, 138, 153, and 180 (ΣPCB4)] and p,p´-DDE were 0.19 (0.01–2.59) and 0.31 (0–14.93) ng/g serum, respectively.
Results: We detected associations between PCBs and neuropsychological deficits for 578 and 584 children with CPT and WISC-III measures, respectively, but only among boys. For example, boys with higher exposure to ΣPCB4 had a higher rate of CPT errors of omission [rate ratio for the exposure interquartile range (IQR) = 1.12; 95% confidence interval (CI): 0.98, 1.27] and slower WISC-III Processing Speed (change in score for the IQR = –2.0; 95% CI: –3.5, –0.4). Weaker associations were found for p,p´-DDE. For girls, associations were in the opposite direction for the CPT and null for the WISC-III.
Conclusions: These results support an association between organochlorines (mainly PCBs) and neuropsychological measures of attention among boys only. Sex-specific effects should be considered in studies of organochlorines and neurodevelopment.
PMCID: PMC3385436  PMID: 22357172
attention deficit hyperactivity disorder; p,p´-dichlorodiphenyl dichloroethylene (p,p´-DDE); epidemiology; maternal exposure; organochlorines; polychlorinated biphenyls (PCBs)
2.  Changes in the Heterodera glycines Female Index as Affected by Ten-year Cropping Sequences 
Journal of Nematology  1994;26(4):505-510.
The objective of this experiment was to measure the change in female index (FI) of Heterodera glycines from bioassays on Bedford, Peking, PI 89772, and PI 90763 soybean (Glycine max) for 12 cropping sequence treatments over a 10-year period. Cropping sequences included continuous plantings of Forrest, Peking, and D72-8927 soybean (all resistant to race 3); Bedford, Nathan, and D75-10710 soybean (all resistant to races 3 and 14); a Bedford-corn (Zea mays) rotation; a rotation of Bedford, Essex (susceptible), and Forrest; and a 70:30 blend of Bedford and Forrest. The FI from bioassays with PI 89772 and PI 90763 decreased over time from 24.3 to 1.6 with treatments involving continuous Bedford, Nathan, and D75-10710 and the Bedford-corn rotation. The FI increased in bioassays using Bedford with treatments involving Bedford, Nathan, D75-10710, the Bedford-Forrest blend, and the two rotations. Results of this field experiment confirm greenhouse experiments in which reciprocal changes occur in FI on PI 89772 and PI 90673 compared with FI on Bedford.
PMCID: PMC2619517  PMID: 19279922
cropping sequence; genetics; Glycine max; Heterodera glycines; nematode; race; resistance; rotation; soybean; soybean cyst nematode
3.  Natural Ventilation for the Prevention of Airborne Contagion 
PLoS Medicine  2007;4(2):e68.
Institutional transmission of airborne infections such as tuberculosis (TB) is an important public health problem, especially in resource-limited settings where protective measures such as negative-pressure isolation rooms are difficult to implement. Natural ventilation may offer a low-cost alternative. Our objective was to investigate the rates, determinants, and effects of natural ventilation in health care settings.
Methods and Findings
The study was carried out in eight hospitals in Lima, Peru; five were hospitals of “old-fashioned” design built pre-1950, and three of “modern” design, built 1970–1990. In these hospitals 70 naturally ventilated clinical rooms where infectious patients are likely to be encountered were studied. These included respiratory isolation rooms, TB wards, respiratory wards, general medical wards, outpatient consulting rooms, waiting rooms, and emergency departments. These rooms were compared with 12 mechanically ventilated negative-pressure respiratory isolation rooms built post-2000. Ventilation was measured using a carbon dioxide tracer gas technique in 368 experiments. Architectural and environmental variables were measured. For each experiment, infection risk was estimated for TB exposure using the Wells-Riley model of airborne infection. We found that opening windows and doors provided median ventilation of 28 air changes/hour (ACH), more than double that of mechanically ventilated negative-pressure rooms ventilated at the 12 ACH recommended for high-risk areas, and 18 times that with windows and doors closed (p < 0.001). Facilities built more than 50 years ago, characterised by large windows and high ceilings, had greater ventilation than modern naturally ventilated rooms (40 versus 17 ACH; p < 0.001). Even within the lowest quartile of wind speeds, natural ventilation exceeded mechanical (p < 0.001). The Wells-Riley airborne infection model predicted that in mechanically ventilated rooms 39% of susceptible individuals would become infected following 24 h of exposure to untreated TB patients of infectiousness characterised in a well-documented outbreak. This infection rate compared with 33% in modern and 11% in pre-1950 naturally ventilated facilities with windows and doors open.
Opening windows and doors maximises natural ventilation so that the risk of airborne contagion is much lower than with costly, maintenance-requiring mechanical ventilation systems. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection. Natural ventilation costs little and is maintenance free, and is particularly suited to limited-resource settings and tropical climates, where the burden of TB and institutional TB transmission is highest. In settings where respiratory isolation is difficult and climate permits, windows and doors should be opened to reduce the risk of airborne contagion.
In eight hospitals in Lima, opening windows and doors maximised natural ventilation and lowered the risk of airborne infection. Old-fashioned clinical areas with high ceilings and large windows provide greatest protection.
Editors' Summary
Tuberculosis (TB) is a major cause of ill health and death worldwide, with around one-third of the world's population infected with the bacterium that causes it (Mycobacterium tuberculosis). One person with active tuberculosis can go on to infect many others; the bacterium is passed in tiny liquid droplets that are produced when someone with active disease coughs, sneezes, spits, or speaks. The risk of tuberculosis being transmitted in hospital settings is particularly high, because people with tuberculosis are often in close contact with very many other people. Currently, most guidelines recommend that the risk of transmission be controlled in certain areas where TB is more likely by making sure that the air in rooms is changed with fresh air between six and 12 times an hour. Air changes can be achieved with simple measures such as opening windows and doors, or by installing mechanical equipment that forces air changes and also keeps the air pressure in an isolation room lower than that outside it. Such “negative pressure,” mechanically ventilated systems are often used on tuberculosis wards to prevent air flowing from isolation rooms to other rooms outside, and so to prevent people on the tuberculosis ward from infecting others.
Why Was This Study Done?
In many parts of the world, hospitals do not have equipment even for simple air conditioning, let alone the special equipment needed for forcing high air changes in isolation rooms and wards. Instead they rely on opening windows and doors in order to reduce the transmission of TB, and this is called natural ventilation. However, it is not clear whether these sorts of measures are adequate for controlling TB transmission. It is important to find out what sorts of systems work best at controlling TB in the real world, so that hospitals and wards can be designed appropriately, within available resources.
What Did the Researchers Do and Find?
This study was based in Lima, Peru's capital city. The researchers studied a variety of rooms, including tuberculosis wards and respiratory isolation rooms, in the city's hospitals. Rooms which had only natural measures for encouraging airflow were compared with mechanically ventilated, negative pressure rooms, which were built much more recently. A comparison was also done between rooms in old hospitals that were naturally ventilated with rooms in newer hospitals that were also naturally ventilated. The researchers used a particular method to measure the number of air changes per hour within each room, and based on this they estimated the risk of a person with TB infecting others using a method called the Wells-Riley equation. The results showed that natural ventilation provided surprisingly high rates of air exchange, with an average of 28 air changes per hour. Hospitals over 50 years old, which generally had large windows and high ceilings, had the highest ventilation, with an average of 40 air changes per hour. This rate compared with 17 air changes per hour in naturally ventilated rooms in modern hospitals, which tended to have lower ceilings and smaller windows. The rooms with modern mechanical ventilation were supposed to have 12 air changes per hour but in reality this was not achieved, as the systems were not maintained properly. The Wells-Riley equation predicted that if an untreated person with tuberculosis was exposed to other people, within 24 hours this person would infect 39% of the people in the mechanically ventilated room, 33% of people in the naturally ventilated new hospital rooms, and only 11% of the people in the naturally ventilated old hospital rooms.
What Do These Findings Mean?
These findings suggest that natural methods of encouraging airflow (e.g., opening doors and windows) work well and in theory could reduce the likelihood of TB being carried from one person to another. Some aspects of the design of wards in old hospitals (such as large windows and high ceilings) are also likely to achieve better airflow and reduce the risk of infection. In poor countries, where mechanical ventilation systems might be too expensive to install and maintain properly, rooms that are designed to naturally achieve good airflow might be the best choice. Another advantage of natural ventilation is that it is not restricted by cost to just high-risk areas, and can therefore be used in many different parts of the hospital, including emergency departments, outpatient departments, and waiting rooms, and it is here that many infectious patients are to be found.
Additional Information.
Please access these Web sites via the online version of this summary at
Information from the World Health Organization on tuberculosis, detailing global efforts to prevent the spread of TB
The World Health Organization publishes guidelines for the prevention of TB in health care facilities in resource-limited settings
Tuberculosis infection control in the era of expanding HIV care and treatment is discussed in an addendum to the above booklet
The Centers for Disease Control have published guidelines for preventing the transmission of mycobacterium tuberculosis in health care settings
Wikipedia has an entry on nosocomial infections (diseases that are spread in hospital). Wikipedia is an internet encyclopedia anyone can edit
A PLoS Medicine Perspective by Peter Wilson, “Is Natural Ventilation a Useful Tool to Prevent the Airborne Spread of TB?” discusses the implications of this study
PMCID: PMC1808096  PMID: 17326709
4.  Housing and Environment for Dairy Calves 
Many cases of poor health in calves have been traced to bad management and inadequate ventilation in the calf nursery. Important management principles for improved calf health include calf housing isolated from the adult herd and periodic depopulation and sanitizing of the calf nursery area. In good weather, low-cost calf rearing portables such as the “calf hutch” can provide alternative housing during the cleanup period.
Calf nursery ventilation systems must have flexibility to give the full winter-to-summer range of controlled ventilation rates and critical air inlet adjustments. Earlier recommendations were for three stepped ventilation rates of 3.3, 6.6 and 24 L/s per calf to cover the range from cold winter to warm summer weather. Later recommendations are for a simpler two stepped fan system starting at 6.7 L/s (continuous winter rate) and increasing to 50 L/s for temperature control in warm to hot weather.
Even with the best insulated construction, increased supplementary heating is required to support this increased continuous winter ventilation. To save energy the heating must be controlled to stop before the higher-rate ventilation starts. Other design features for more uniform temperatures and improved calf nursery ventilation include: 1) preheating the ventilation air before it enters the calf room, 2) distributing air to the ceiling with round holes and adjustable slots adjusted to give at least 4 m/s inlet velocity, 3) using a properly sized centrifugal fan running continuously to exhaust air from near the floor in winter and 4) protecting air intakes and fan openings from the effects of wind. Air recirculation systems and variable-speed fans are not recommended.
PMCID: PMC1789686  PMID: 7363271
5.  Conventional mechanical ventilation 
Saudi Journal of Anaesthesia  2010;4(2):86-98.
The provision of mechanical ventilation for the support of infants and children with respiratory failure or insufficiency is one of the most common techniques that are performed in the Pediatric Intensive Care Unit (PICU). Despite its widespread application in the PICUs of the 21st century, before the 1930s, respiratory failure was uniformly fatal due to the lack of equipment and techniques for airway management and ventilatory support. The operating rooms of the 1950s and 1960s provided the arena for the development of the manual skills and the refinement of the equipment needed for airway management, which subsequently led to the more widespread use of endotracheal intubation thereby ushering in the era of positive pressure ventilation. Although there seems to be an ever increasing complexity in the techniques of mechanical ventilation, its successful use in the PICU should be guided by the basic principles of gas exchange and the physiology of respiratory function. With an understanding of these key concepts and the use of basic concepts of mechanical ventilation, this technique can be successfully applied in both the PICU and the operating room. This article reviews the basic physiology of gas exchange, principles of pulmonary physiology, and the concepts of mechanical ventilation to provide an overview of the knowledge required for the provision of conventional mechanical ventilation in various clinical arenas.
PMCID: PMC2945520  PMID: 20927268
Mechanical ventilation; respiratory failure; ventilatory support
6.  Design and Evaluation of a Ventilated Garment for Use in Temperatures up to 200°C 
The protection of personnel against high air and radiant temperatures is a problem that has been confronting industry for many years now, and for many industrial situations it still has not been solved. The experiments reported here were intended to determine the most suitable form of insulation for a hot entry suit for use primarily in furnace wrecking where mean radiant temperatures of 200°C. are met and where heat-reflecting garments are unsuitable due to the rapid deterioration of the reflecting surface.
From a preliminary consideration of the problem it was concluded that a ventilated garment was required and that conventional ventilated garments in which air is induced to flow parallel to the body surfaces (axial ventilation) are basically unsound in design as the air is not utilized for the transfer of heat in the most efficient manner. A new form of ventilation was therefore developed in which air flows out through a permeable suit (radial ventilation). This form of ventilation produces what is called dynamic insulation, and this method of insulation, when compared with two alternative methods on a physical model, was found to be very effective.
The model experiments were confirmed by comparative trials of three ventilated suits each using one of three different forms of insulation thought to be suitable for use in heat-protective clothing.
Physiological measurements made on the subjects and physical measurement made on the suits confirmed that dynamic insulation is the most suitable insulation for a hot entry suit for furnace wrecking.
With the air flows used in these experiments, dynamic insulation had a thermal conductance one-fifth that of conventional static insulation, and sweat losses and oral temperature rises were reduced by one-third and one-half respectively.
PMCID: PMC1038354  PMID: 14180476
7.  A new device for 100 per cent humidification of inspired air 
Critical Care  2000;4(1):54-60.
A new humidifier for use during mechanical ventilation in endotracheally intubated patients is described and tested. The humidifier is based on a heat-moisture exchanger, which absorbs the expired heat and moisture and releases it into the inspired air. External heat and water are then added at the patient side of the heat-moisture exchanger, so that the inspired gas should reach 100% humidity (44 mg/l) at 37°C. In bench tests using constant and decelerating inspiratory flow and minute volumes of 3–25 l the device gave an absolute humidity of 41–44 mg/l, and it reduced the amount of water consumed in eight mechanically ventilated patients compared with a conventional active humidifier. During a 24-h test period there was no water condensation in the ventilator tubing with the new device.
Devices for active humidification of the inspired air in mechanically ventilated patients cause water condensation in the ventilator tubing, which may become contaminated or interfere with the function of the ventilator. The present study describes and tests the performance of a new humidifier, which is designed to eliminate water condensation.
To test the performance of the new humidifier at different ventilator settings in a lung model, and to compare this new humidifier with a conventional active humidifier in ventilator-treated critically ill patients.
Materials and methods:
The humidifier (Humid-Heat; Louis Gibeck AB, Upplands Väsby, Sweden) consists of a supply unit with a microprocessor and a water pump, and a humidification device, which is placed between the Y-piece and the endotracheal tube. The humidification device is based on a hygroscopic heat-moisture exchanger (HME), which absorbs the expired heat and moisture and releases it into the inspired gas. External heat and water are then added to the patient side of the HME, so the inspired gas should reach 100% humidity at 37°C (44 mg H2O/l air). The external water is delivered to the humidification device via a pump onto a wick and then evaporated into the inspired air by an electrical heater. The microprocessor controls the water pump and the heater by an algorithm using the minute ventilation (which is fed into the microprocessor) and the airway temperature measured by a sensor mounted in the flex-tube on the patient side of the humidification device.
The performance characteristics were tested in a lung model ventilated with a constant flow (inspiratory:expiratory ratio 1:2, rate 12–20 breaths/min and a minute ventilation of 3–25 l/min) or with a decelerating flow (inspiratory:expiratory ratio 1:2, rate 12–15 breaths/min and a minute ventilation of 4.7–16.4 l/min). The device was also tested prospectively and in a randomized order compared with a conventional active humidifier (Fisher & Paykel MR730, Auckland, New Zealand) in eight mechanically ventilated, endotracheally intubated patients in the intensive care unit. The test period with each device was 24 h. The amount of fluid consumed and the amount of water in the water traps were measured. The number of times that the water traps were emptied, changes of machine filters, the suctions and quality of secretions, nebulizations, and the amount of saline instillations and endotracheal tube obstruction were recorded. In order to evaluate increased expiratory resistance due to the device, the airway pressure was measured at the end of a prolonged end-expiratory pause at 1 h of use and at the end of the test, and was compared with the corresponding pressure before the experiment. The body temperature of the patient was measured before and after the test of each device.
Both with constant flow and decelerating flow, the Humid-Heat gave an absolute humidity of 41–44 mgH2O/l at 37°C, with the lower level at the highest ventilation. In the patients, both Humid-Heat and the conventional active humidifier (MR730) maintained temperatures, indicating that they provided the intended heat and moisture to the inspired air. With both devices, the body temperature was maintained during the test period. There was no difference in the amount of secretions, the quality of the secretions and the frequency of suctions, saline instillations or nebulizations between the test periods with the two devices. There was no endotracheal tube obstruction, and after 1 h of use and at the end of the test no increased airway resistance was found with either device. When the MR730 was used, however, the water traps needed to be emptied six to 14 (mean eight) times (total amount of fluid in the traps was 100–300 ml) and the machine filters were changed two to six (mean four) times due to an excessive amount of condensed water with flow obstruction. No condensation of water was found in the tubing with the Humid-Heat. The water consumption was 23–65 ml/h (mean 30 ml/h) with the MR730 and 4–8 ml/h (mean 6 ml/h) with the Humid-Heat (P < 0.0008). The same relations were found when the water consumption was corrected for differences in minute ventilation.
The new humidifier, the Humid-Heat, gave an absolute humidity of 41–44 mg/l at 37°C in the bench tests. The tests in ventilated patients showed that the device was well tolerated and that condensation in the tubing was eliminated. There was no need to empty water traps. The test period was too short to evaluate whether the new device had any other advantages or disadvantages compared with conventional humidifiers.
PMCID: PMC29037  PMID: 11056746
airway humidification; heated humidifier; intensive care; mechanical ventilation
Biology of Sport  2014;31(2):145-149.
The aim of the paper was to follow up major physiological reactions, provoked by heat stress during dry and wet sauna baths. A physical strain index and subjective estimation of heat comfort of subjects who had not taken sauna baths before was also evaluated. Ten healthy males aged 25-28 underwent a dry sauna bath and then after a one-month break they underwent a steam sauna bath. Each time, they entered the sauna chamber 3 times for 15 minutes with five-minute breaks. During breaks they cooled their bodies with a cold shower and then rested in a sitting position. Before and after the baths, body mass and blood pressure were measured. Rectal temperature and heart rate were monitored during the baths. The physiological strain index (PSI) and cumulative heat strain index (CHSI) were calculated. Subjects assessed heat comfort by Bedford's scale. Greater body mass losses were observed after the dry sauna bath compared to the wet sauna (-0.72 vs. -0.36 kg respectively). However, larger increases in rectal temperature and heart rate were observed during the wet sauna bath (38.8% and 21.2% respectively). Both types of sauna baths caused elevation of systolic blood pressure, but changes were greater after the dry one. Diastolic pressure was reduced similarly. Subjective feelings of heat comfort as well as PSI (4.83 ± 0.29 vs. 5.7 ± 0.28) and CHSI (76.3 ± 18.4 vs. 144.6 ± 21.7) were greater during the wet sauna bath. It can be concluded that due to high humidity and reduction of thermoregulation mechanisms, the wet sauna is more stressful for the organism than the dry sauna, where the temperature is higher with low humidity. Both observed indexes (PSI and CHSI) could be appropriate for objective assessment of heat strain during passive heating of the organism.
PMCID: PMC4042662  PMID: 24899780
finnish sauna; wet steam bath; heat stress indexes
9.  Elective ventilation for organ donation: law, policy and public ethics 
Journal of Medical Ethics  2012;39(3):130-134.
This paper examines questions concerning elective ventilation, contextualised within English law and policy. It presents the general debate with reference both to the Exeter Protocol on elective ventilation, and the considerable developments in legal principle since the time that that protocol was declared to be unlawful. I distinguish different aspects of what might be labelled elective ventilation policies under the following four headings: ‘basic elective ventilation’; ‘epistemically complex elective ventilation’; ‘practically complex elective ventilation’; and ‘epistemically and practically complex elective ventilation’. I give a legal analysis of each. In concluding remarks on their potential practical viability, I emphasise the importance not just of ascertaining the legal and ethical acceptability of these and other forms of elective ventilation, but also of assessing their professional and political acceptability. This importance relates both to the successful implementation of the individual practices, and to guarding against possible harmful effects in the wider efforts to increase the rates of posthumous organ donation.
PMCID: PMC3948088  PMID: 23222143
Prolongation of Life and Euthanasia; Public Policy; Donation/Procurement of Organs/Tissues; Applied and Professional Ethics; Care of the Dying Patient
10.  PREP-Mt: predictive RNA editor for plant mitochondrial genes 
BMC Bioinformatics  2005;6:96.
In plants, RNA editing is a process that converts specific cytidines to uridines and uridines to cytidines in transcripts from virtually all mitochondrial protein-coding genes. There are thousands of plant mitochondrial genes in the sequence databases, but sites of RNA editing have not been determined for most. Accurate methods of RNA editing site prediction will be important in filling in this information gap and could reduce or even eliminate the need for experimental determination of editing sites for many sequences. Because RNA editing tends to increase protein conservation across species by "correcting" codons that specify unconserved amino acids, this principle can be used to predict editing sites by identifying positions where an RNA editing event would increase the conservation of a protein to homologues from other plants. PREP-Mt takes this approach to predict editing sites for any protein-coding gene in plant mitochondria.
To test the general applicability of the PREP-Mt methodology, RNA editing sites were predicted for 370 full-length or nearly full-length DNA sequences and then compared to the known sites of RNA editing for these sequences. Of 60,263 cytidines in this test set, PREP-Mt correctly classified 58,994 as either an edited or unedited site (accuracy = 97.9%). PREP-Mt properly identified 3,038 of the 3,698 known sites of RNA editing (sensitivity = 82.2%) and 55,956 of the 56,565 known unedited sites (specificity = 98.9%). Accuracy and sensitivity increased to 98.7% and 94.7%, respectively, after excluding the 489 silent editing sites (which have no effect on protein sequence or function) from the test set.
These results indicate that PREP-Mt is effective at identifying C to U RNA editing sites in plant mitochondrial protein-coding genes. Thus, PREP-Mt should be useful in predicting protein sequences for use in molecular, biochemical, and phylogenetic analyses. In addition, PREP-Mt could be used to determine functionality of a mitochondrial gene or to identify particular sequences with unusual editing properties. The PREP-Mt methodology should be applicable to any system where RNA editing increases protein conservation across species.
PMCID: PMC1087475  PMID: 15826309
11.  Community-Wide Health Risk Assessment Using Geographically Resolved Demographic Data: A Synthetic Population Approach 
PLoS ONE  2014;9(1):e87144.
Evaluating environmental health risks in communities requires models characterizing geographic and demographic patterns of exposure to multiple stressors. These exposure models can be constructed from multivariable regression analyses using individual-level predictors (microdata), but these microdata are not typically available with sufficient geographic resolution for community risk analyses given privacy concerns.
We developed synthetic geographically-resolved microdata for a low-income community (New Bedford, Massachusetts) facing multiple environmental stressors. We first applied probabilistic reweighting using simulated annealing to data from the 2006–2010 American Community Survey, combining 9,135 microdata samples from the New Bedford area with census tract-level constraints for individual and household characteristics. We then evaluated the synthetic microdata using goodness-of-fit tests and by examining spatial patterns of microdata fields not used as constraints. As a demonstration, we developed a multivariable regression model predicting smoking behavior as a function of individual-level microdata fields using New Bedford-specific data from the 2006–2010 Behavioral Risk Factor Surveillance System, linking this model with the synthetic microdata to predict demographic and geographic smoking patterns in New Bedford.
Our simulation produced microdata representing all 94,944 individuals living in New Bedford in 2006–2010. Variables in the synthetic population matched the constraints well at the census tract level (e.g., ancestry, gender, age, education, household income) and reproduced the census-derived spatial patterns of non-constraint microdata. Smoking in New Bedford was significantly associated with numerous demographic variables found in the microdata, with estimated tract-level smoking rates varying from 20% (95% CI: 17%, 22%) to 37% (95% CI: 30%, 45%).
We used simulation methods to create geographically-resolved individual-level microdata that can be used in community-wide exposure and risk assessment studies. This approach provides insights regarding community-scale exposure and vulnerability patterns, valuable in settings where policy can be informed by characterization of multi-stressor exposures and health risks at high resolution.
PMCID: PMC3904963  PMID: 24489855
12.  Hyperoxic Brain Effects Are Normalized by Addition of CO2 
PLoS Medicine  2007;4(5):e173.
Hyperoxic ventilation (>21% O2) is widely used in medical practice for resuscitation, stroke intervention, and chronic supplementation. However, despite the objective of improving tissue oxygen delivery, hyperoxic ventilation can accentuate ischemia and impair that outcome. Hyperoxia results in, paradoxically, increased ventilation, which leads to hypocapnia, diminishing cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces other systemic changes, including increased plasma insulin and glucagon levels and reduced myocardial contractility and relaxation, which may derive partially from neurally mediated hormonal and sympathetic outflow. Several cortical, limbic, and cerebellar brain areas regulate these autonomic processes. The aim of this study was to assess recruitment of these regions in response to hyperoxia and to determine whether any response would be countered by addition of CO2 to the hyperoxic gas mixture.
Methods and Findings
We studied 14 children (mean age 11 y, range 8–15 y). We found, using functional magnetic resonance imaging, that 2 min of hyperoxic ventilation (100% O2) following a room air baseline elicited pronounced responses in autonomic and hormonal control areas, including the hypothalamus, insula, and hippocampus, throughout the challenge. The addition of 5% CO2 to 95% O2 abolished responses in the hypothalamus and lingual gyrus, substantially reduced insular, hippocampal, thalamic, and cerebellar patterns in the first 48 s, and abolished signals in those sites thereafter. Only the dorsal midbrain responded to hypercapnia, but not hyperoxia.
In this group of children, hyperoxic ventilation led to responses in brain areas that modify hypothalamus-mediated sympathetic and hormonal outflow; these responses were diminished by addition of CO2 to the gas mixture. This study in healthy children suggests that supplementing hyperoxic administration with CO2 may mitigate central and peripheral consequences of hyperoxia.
Hyperoxic ventilation leads to responses in brain areas that modify hypothalamus-mediated sympathetic and hormonal outflow; these responses can be diminished by addition of CO2 to the gas mixture.
Editors' Summary
All cells in the human body need oxygen (O2) to keep them alive. O2 is absorbed into the blood from the air by the lungs (which also release carbon dioxide [CO2], a waste product of cells, from the blood into the air). The blood then delivers O2 to the rest of the body. For healthy people, breathing air (which contains 21% O2) is sufficient to keep their tissues healthy. But there are medical situations in which O2 delivery to tissues needs improving. For example, during resuscitation or after a stroke when the O2 supply to a part of the brain is disrupted. Premature babies often need help with O2 delivery because their immature lungs don't absorb O2 efficiently. In situations like these, the O2 supply can be increased by providing an O2-rich gas mixture to the lungs—so-called “hyperoxic (i.e., high O2) ventilation.” But, paradoxically, hyperoxic ventilation can make matters worse. Hyperoxia increases the exchange of air between the lungs and the atmosphere (hyperventilation), which reduces the CO2 level in the blood. This “hypocapnia,” i.e. low CO2, reduces the blood flow to the brain by narrowing the blood vessels. Hyperoxia also alters the heart rate and blood pressure and the blood levels of some hormones. It probably causes these changes by affecting the brain regions that control autonomic functions (body functions such as heart rate, insulin and other hormone release, sweating and gland action that are not controlled by conscious thought). All told, although hyperoxic ventilation saves lives, it can also have serious adverse effects. In premature babies, for example, although it is often essential for their survival, hyperoxic ventilation can cause serious heart muscle and brain injury or lung problems (bronchopulmonary dysplasia) if it is not carefully monitored.
Why Was This Study Done?
The addition of a little CO2 to the hyperoxic gas mix can reduce the adverse effects of hyperoxic ventilation on blood flow to the brain. However, it is unclear whether this alteration can also modify responses of brain areas that control autonomic functions and hormone release to hyperoxia. If it does, then CO2 supplementation could prevent those adverse effects of hyperoxic ventilation that affect the whole body. In this study, the researchers investigated whether hyperoxic ventilation increases neural responses in brain regions that regulate the activity of the hypothalamus (the part of the brain that controls autonomic bodily functions) and whether the addition of CO2 reduces these responses.
What Did the Researchers Do and Find?
The researchers used a technique called functional magnetic resonance imaging (fMRI) to measure the activity of different brain regions in 14 healthy young people (aged 8–15 years). Active regions of the brain draw more O2 out of the blood than inactive regions, and fMRI measures changes in blood O2 levels. fMRI images were obtained for all the study participants when they were breathing normal air and during two-minute challenges with 100% O2 or a 95% O2, 5% CO2 mix. Hyperoxic ventilation produced rapid and marked changes in the activity of brain areas involved in autonomic and hormonal control, including the hypothalamus and regions that control the hypothalamus. After the challenge with 95% O2, 5% CO2, these responses were either absent or greatly reduced in the brain regions that had responded to 100% O2.
What Do These Findings Mean?
These findings show that hyperoxic ventilation induces brain activity changes that are likely to affect autonomic functions and hormone release throughout the body. In addition, they show that the addition of CO2 to the gas mixture greatly diminishes these responses. Because the autonomic and hormonal changes induced by 100% O2 can potentially injure organs throughout the body, the addition of CO2 to hyperoxic gas mixtures could reduce many of the adverse effects of hyperoxic ventilation. These results, therefore, could influence how hyperoxic ventilation is used in medical practice. However, CO2 supplementation still needs to be tested in adults and newborn babies. Although the results presented here will probably hold true for adults, and both neonatal and developmental animal studies suggest that hyperoxia results in serious side effects in newborns over room air or hyperoxia with added CO2, the brain findings need to studied in babies, the portion of the population most likely to be treated with hyperoxic ventilation.
Additional Information.
Please access these Web sites via the online version of this summary at
The American Lung Association has patient information on the lungs and lung diseases, including bronchopulmonary dysplasia (in English and Spanish)
The Medlineplus encyclopedia contains pages on hyperventilation and on premature babies, and links to other information on premature babies (in English and Spanish)
Wikipedia has pages on the lungs, oxygen toxicity, mechanical ventilation, and hypocapnia (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
PMCID: PMC1872042  PMID: 17518514
13.  Exhaled Breath Condensate Collection in the Mechanically Ventilated Patient 
Respiratory Medicine  2012;106(5):601-613.
Collection of exhaled breath condensate (EBC) is a non-invasive means of sampling the airway-lining fluid of the lungs. EBC contains numerous measurable mediators, whose analysis could change the management of patients with certain pulmonary diseases.
While initially popularized in investigations involving spontaneously breathing patients, an increasing number of studies have been performed using EBC in association with mechanical ventilation. Collection of EBC in mechanically ventilated patients follows basic principles of condensation, but is influenced by multiple factors. Effective collection requires selection of a collection device, adequate minute ventilation, low cooling temperatures, and sampling times of greater than ten minutes. Condensate can be contaminated by saliva, which needs to be filtered. Dilution of samples occurs secondary to distilled water in vapors and humidification in the ventilator circuit. Dilution factors may need to be employed when investigating non-volatile biomarkers. Storage and analysis should occur promptly at −70° C to −80° C to prevent rapid degradation of samples.
The purpose of this review is to examine and describe methodologies and problems of EBC collection in mechanically ventilated patients. A straightforward and safe framework has been established to investigate disease processes in this population, yet technical aspects of EBC collection still exist that prevent clinical practicality of this technology. These include a lack of standardization of procedure and analysis of biomarkers, and of normal reference ranges for mediators in healthy individuals. Once these procedural aspects have been addressed, EBC could serve as a non-invasive alternative to invasive evaluation of lungs in mechanically ventilated patients.
PMCID: PMC3314159  PMID: 22398157
Exhaled breath condensate; Biomarkers; Inflammation; Mechanical ventilation; Airway-lining fluid
14.  Direct detection of Mycobacterium tuberculosis in sputum by polymerase chain reaction and DNA hybridization. 
Journal of Clinical Microbiology  1993;31(7):1777-1782.
A polymerase chain reaction (PCR) assay for the rapid diagnosis of pulmonary tuberculosis was developed by using oligonucleotide primers to amplify a fragment of IS6110, an insertion sequence repeated multiple times in the chromosome of Mycobacterium tuberculosis. Sediment obtained from sputa processed by the N-acetyl-L-cysteine-NaOH method was suspended in a simple lysis buffer and was heated at 100 degrees C for 30 min prior to amplification. A dUTP-uracil N-glycosylase PCR protocol was used to prevent false-positive test results because of the carryover of products from previous amplification reactions. The 317-bp amplicon was detected by direct gel analysis and Southern blotting and then hybridization with a biotin-labeled internal probe. Hybrid molecules were detected by using a commercially available avidin-alkaline phosphatase-chemiluminescent substrate system (Tropix, Inc., Bedford, Mass.). The analytical sensitivity of the assay was 10 fg of purified mycobacterial DNA. The limits of detection by culture (Middlebrook 7H11 agar and Lowenstein-Jensen medium) and by PCR were equivalent in terminal dilution experiments for organism suspensions and positive sputa. An internal control was used to detect the presence of amplification inhibitors in each negative reaction mixture. DNA was purified from inhibitory specimens by phenol-chloroform extraction and ethanol precipitation. PCR results were compared with results of microscopy and conventional culture for the detection of M. tuberculosis in 313 sputum specimens. There were 124 specimens that were positive for M. tuberculosis by conventional methods and 113 (91%) that were positive by PCR. PCR detected 105 of 110 (95%) of the smear-positive and 8 of 14 (57%) of the smear-negative specimens. There were no false-positive results by PCR (specificity, 100%). This PCR assay innovations that make application of this new technology feasible in clinical microbiology laboratories.
PMCID: PMC265631  PMID: 8349753
15.  Invasive home mechanical ventilation, mainly focused on neuromuscular disorders 
Introduction and background
Invasive home mechanical ventilation is used for patients with chronic respiratory insufficiency. This elaborate and technology-dependent ventilation is carried out via an artificial airway (tracheal cannula) to the trachea. Exact numbers about the incidence of home mechanical ventilation are not available. Patients with neuromuscular diseases represent a large portion of it.
Research questions
Specific research questions are formulated and answered concerning the dimensions of medicine/nursing, economics, social, ethical and legal aspects. Beyond the technical aspect of the invasive home, mechanical ventilation, medical questions also deal with the patient’s symptoms and clinical signs as well as the frequency of complications. Economic questions pertain to the composition of costs and the differences to other ways of homecare concerning costs and quality of care. Questions regarding social aspects consider the health-related quality of life of patients and caregivers. Additionally, the ethical aspects connected to the decision of home mechanical ventilation are viewed. Finally, legal aspects of financing invasive home mechanical ventilation are discussed.
Based on a systematic literature search in 2008 in a total of 31 relevant databases current literature is viewed and selected by means of fixed criteria. Randomized controlled studies, systematic reviews and HTA reports (health technology assessment), clinical studies with patient numbers above ten, health-economic evaluations, primary studies with particular cost analyses and quality-of-life studies related to the research questions are included in the analysis.
Results and discussion
Invasive mechanical ventilation may improve symptoms of hypoventilation, as the analysis of the literature shows. An increase in life expectancy is likely, but for ethical reasons it is not confirmed by premium-quality studies. Complications (e. g. pneumonia) are rare. Mobile home ventilators are available for the implementation of the ventilation. Their technical performance however, differs regrettably.
Studies comparing the economic aspects of ventilation in a hospital to outpatient ventilation, describe home ventilation as a more cost-effective alternative to in-patient care in an intensive care unit, however, more expensive in comparison to a noninvasive (via mask) ventilation. Higher expenses arise due to the necessary equipment and the high expenditure of time for the partial 24-hour care of the affected patients through highly qualified personnel. However, none of the studies applies to the German provisionary conditions. The calculated costs strongly depend on national medical fees and wages of caregivers, which barely allows a transmission of the results.
The results of quality-of-life studies are mostly qualitative. The patient’s quality of life using mechanical ventilation is predominantly considered well. Caregivers of ventilated patients report positive as well as negative ratings. Regarding the ethical questions, it was researched which aspects of ventilation implementation will have to be considered.
From a legal point of view the financing of home ventilation, especially invasive mechanical ventilation, requiring specialised technical nursing is regulated in the code of social law (Sozialgesetzbuch V). The absorption of costs is distributed to different insurance carriers, who often, due to cost pressures within the health care system, insurance carriers, who consider others and not themselves as responsible. Therefore in practice, the necessity to enforce a claim of cost absorption often arises in order to exercise the basic right of free choice of location.
Positive effects of the invasive mechanical ventilation (overall survival and symptomatic) are highly probable based on the analysed literature, although with a low level of evidence. An establishment of a home ventilation registry and health care research to ascertain valid data to improve outpatient structures is necessary. Gathering specific German data is needed to adequately depict the national concepts of provision and reimbursement. A differentiation of the cost structure according to the type of chosen outpatient care is currently not possible. There is no existing literature concerning the difference of life quality depending on the chosen outpatient care (homecare, assisted living, or in a nursing home specialised in invasive home ventilation). Further research is required.
For a so called participative decision – made by the patient after intense counselling – an early and honest patient education pro respectively contra invasive mechanical ventilation is needed. Besides the long term survival, the quality of life and individual, social and religious aspects have also to be considered.
PMCID: PMC3010883  PMID: 21289881
home ventilation; invasive ventilation; extra-clinical ventilation; mechanical ventilation; neuromuscular disease; respiratory insufficience; vital capacity; Health Technology Assessment; HTA; economic analysis; ethics; psychologic pressure; quality of life; health related quality of life
16.  Changes in Reproduction of a Heterodera glycines Race 5 Isolate Cultured on 'Cordell' and 'Bedford' Soybean 
Journal of Nematology  1994;26(4S):653-655.
Isolates from a race 5 field population of Heterodera glycines were cultured separately on soybean cultivars 'Bedford' (resistance derived from Peking and plant introduction [PI] 88788) and 'Cordell' (resistance derived from 'Peking', PI 88788, and PI 90763) for 10, 12, and 14 generations. Reproduction was measured of the 10th, 12th, and 14th generations on Bedford and Cordell and on Peking, 'Pickett', PI 88788, PI 90763, and 'Lee' (the soybean lines that are used to determine H. glycines race). The isolate cultured on Bedford remained race 5, whereas the isolate cultured on Cordell changed to race 14, to which Bedford is moderately resistant. Cordell probably derived its race 5 resistance from either Peking or PI 90763 because the isolate resulting from culture on Cordell reproduced on the H. glycines race differentials in a pattern similar to those of other isolates selected on PI 90763 in previous studies. Rotation of cultivars with pedigrees similar to Bedford and Cordell may be effective in managing H. glycines to prevent yield suppression in soybean and the development of new races.
PMCID: PMC2619542  PMID: 19279942
Glycine max; Heterodera glycines; nematode; race; resistance; selection; soybean; soybean cyst nematode
17.  Changes in the Reproduction of Heterodera glycines on Different Lines of Glycine max 
Journal of Nematology  1984;16(3):304-309.
Selection for ability of soybean cyst nematode (SCN), Heterodera glycines, to reproduce on soybeans with different sources of resistance divides some SCN race 4 field populations into two distinct subpopulations. These subpopulations reproduce well on 'Bedford' and plant introduction (PI) 88788 or PI 89772 and PI 90763 but not on both pairs of soybean lines. The ability of these subpopulations to reproduce on the four soybean lines was reversed by changing the soybean line used as a host during a second cycle of selection. When SCN populations previously selected for reproduction on Bedford and PI 88788 were selected for their ability to reproduce on D72-8927 and J74-88, the ability of these populations to reproduce on Bedford and PI 88788 decreased significantly and their ability to reproduce on PI 89772 and PI 90763 increased significantly. Conversely, when SCN populations, previously selected for reproduction on P189772 and P190763, were selected for their ability to reproduce on Bedford, the reproduction of these populations on Bedford increased significantly and reproduction on PI 89772 and PI 90763 decreased significantly. Selection for ability of a SCN race 4 field population to reproduce on soybean lines derived from SCN race 4 resistant PIs resulted in the same division of the field population into two distinct subpopulations. These data substantiate earlier proposals to rotate cultivars with different genes for SCN resistance as a means of managing SCN populations.
PMCID: PMC2618388  PMID: 19294026
races; resistance; soybean; soybean cyst nematode
18.  Host Suitability and Susceptibility of Glycine max cv. Bedford to Race 1 of Heterodera glycines 
Journal of Nematology  1983;15(1):136-139.
Populations of Heterodera glycines identifiable as race 1 reproduced on the race 1 resistant 'Bedford' soybean. A Beaufort County, North Carolina, population had an index of parasitism of 112% on Bedford in greenhouse tests. Indices of parasitism for this population on race 1 resistant cultivars Pickett 71, Centennial, and Forrest were less than 10%. The Beaufort County population had significantly greater reproduction on Bedford in microplots than did populations of race 3 or race 4. In field tests, a race 1 population suppressed yields of Bedford but not yields of Centennial. Based on these data, Bedford is no longer recommended in North Carolina as a race 1 resistant cultivar.
PMCID: PMC2618253  PMID: 19295779
host resistance; soybean cyst nematode; nematode management; soybean; reproduction
19.  Manual Refinement System for Graph-Based Segmentation Results in the Medical Domain 
Journal of medical systems  2011;36(5):2829-2839.
The basic principle of graph-based approaches for image segmentation is to interpret an image as a graph, where the nodes of the graph represent 2D pixels or 3D voxels of the image. The weighted edges of the graph are obtained by intensity differences in the image. Once the graph is constructed, the minimal cost closed set on the graph can be computed via a polynomial time s-t cut, dividing the graph into two parts: the object and the background. However, no segmentation method provides perfect results, so additional manual editing is required, especially in the sensitive field of medical image processing. In this study, we present a manual refinement method that takes advantage of the basic design of graph-based image segmentation algorithms. Our approach restricts a graph-cut by using additional user-defined seed points to set up fixed nodes in the graph. The advantage is that manual edits can be integrated intuitively and quickly into the segmentation result of a graph-based approach. The method can be applied to both 2D and 3D objects that have to be segmented. Experimental results for synthetic and real images are presented to demonstrate the feasibility of our approach.
PMCID: PMC3691109  PMID: 21826501
Segmentation; Graph-based; Manual refinement; 2D; 3D
20.  Health Outcomes and Green Renovation of Affordable Housing 
Public Health Reports  2011;126(Suppl 1):64-75.
This study sought to determine whether renovating low-income housing using “green” and healthy principles improved resident health and building performance.
We investigated resident health and building performance outcomes at baseline and one year after the rehabilitation of low-income housing using Enterprise Green Communities green specifications, which improve ventilation; reduce moisture, mold, pests, and radon; and use sustainable building products and other healthy housing features. We assessed participant health via questionnaire, provided Healthy Homes training to all participants, and measured ventilation, carbon dioxide, and radon.
Adults reported statistically significant improvements in overall health, asthma, and non-asthma respiratory problems. Adults also reported that their children's overall health improved, with significant improvements in non-asthma respiratory problems. Post-renovation building performance testing indicated that the building envelope was tightened and local exhaust fans performed well. New mechanical ventilation was installed (compared with no ventilation previously), with fresh air being supplied at 70% of the American Society of Heating, Refrigerating, and Air-Conditioning Engineers standard. Radon was <2 picocuries per liter of air following mitigation, and the annual average indoor carbon dioxide level was 982 parts per million. Energy use was reduced by 45% over the one-year post-renovation period.
We found significant health improvements following low-income housing renovation that complied with green standards. All green building standards should include health requirements. Collaboration of housing, public health, and environmental health professionals through integrated design holds promise for improved health, quality of life, building operation, and energy conservation.
PMCID: PMC3072905  PMID: 21563714
21.  Anaesthesia ventilators 
Indian Journal of Anaesthesia  2013;57(5):525-532.
Anaesthesia ventilators are an integral part of all modern anaesthesia workstations. Automatic ventilators in the operating rooms, which were very simple with few modes of ventilation when introduced, have become very sophisticated with many advanced ventilation modes. Several systems of classification of anaesthesia ventilators exist based upon various parameters. Modern anaesthesia ventilators have either a double circuit, bellow design or a single circuit piston configuration. In the bellows ventilators, ascending bellows design is safer than descending bellows. Piston ventilators have the advantage of delivering accurate tidal volume. They work with electricity as their driving force and do not require a driving gas. To enable improved patient safety, several modifications were done in circle system with the different types of anaesthesia ventilators. Fresh gas decoupling is a modification done in piston ventilators and in descending bellows ventilator to reduce th incidence of ventilator induced volutrauma. In addition to the conventional volume control mode, modern anaesthesia ventilators also provide newer modes of ventilation such as synchronised intermittent mandatory ventilation, pressure-control ventilation and pressure-support ventilation (PSV). PSV mode is particularly useful for patients maintained on spontaneous respiration with laryngeal mask airway. Along with the innumerable benefits provided by these machines, there are various inherent hazards associated with the use of the ventilators in the operating room. To use these workstations safely, it is important for every Anaesthesiologist to have a basic understanding of the mechanics of these ventilators and breathing circuits.
PMCID: PMC3821270  PMID: 24249886
Anaesthesia ventilators; circle system changes; classification; hazards; working principle
22.  Does a 4 diagram manual enable laypersons to operate the laryngeal mask supreme®? A pilot study in the manikin 
Bystander resuscitation plays an important role in lifesaving cardiopulmonary resuscitation (CPR). A significant reduction in the "no-flow-time", quantitatively better chest compressions and an improved quality of ventilation can be demonstrated during CPR using supraglottic airway devices (SADs). Previous studies have demonstrated the ability of inexperienced persons to operate SADs after brief instruction. The aim of this pilot study was to determine whether an instruction manual consisting of four diagrams enables laypersons to operate a Laryngeal Mask Supreme® (LMAS) in the manikin.
An instruction manual of four illustrations with speech bubbles displaying the correct use of the LMAS was designed. Laypersons were handed a bag containing a LMAS, a bag mask valve device (BMV), a syringe prefilled with air and the instruction sheet, and were asked to perform and ventilate the manikin as displayed. Time to ventilation was recorded and degree of success evaluated.
A total of 150 laypersons took part. Overall 145 participants (96.7%) inserted the LMAS in the manikin in the right direction. The device was inserted inverted or twisted in 13 (8.7%) attempts. Eight (5.3%) individuals recognized this and corrected the position. Within the first 2 minutes 119 (79.3%) applicants were able to insert the LMAS and provide tidal volumes greater than 150 ml (estimated dead space). Time to insertion and first ventilation was 83.2 ± 29 s. No significant difference related to previous BLS training (P = 0.85), technical education (P = 0.07) or gender could be demonstrated (P = 0.25).
In manikin laypersons could insert LMAS in the correct direction after onsite instruction by a simple manual with a high success rate. This indicates some basic procedural understanding and intellectual transfer in principle. Operating errors (n = 91) were frequently not recognized and corrected (n = 77). Improvements in labeling and the quality of instructional photographs may reduce individual error and may optimize understanding.
PMCID: PMC3375204  PMID: 22453060
23.  Lung Function and Incidence of Chronic Obstructive Pulmonary Disease after Improved Cooking Fuels and Kitchen Ventilation: A 9-Year Prospective Cohort Study 
PLoS Medicine  2014;11(3):e1001621.
Pixin Ran, Nanshan Zhong, and colleagues report that cleaner cooking fuels and improved ventilation were associated with better lung function and reduced COPD among a cohort of villagers in Southern China.
Please see later in the article for the Editors' Summary
Biomass smoke is associated with the risk of chronic obstructive pulmonary disease (COPD), but few studies have elaborated approaches to reduce the risk of COPD from biomass burning. The purpose of this study was to determine whether improved cooking fuels and ventilation have effects on pulmonary function and the incidence of COPD.
Methods and Findings
A 9-y prospective cohort study was conducted among 996 eligible participants aged at least 40 y from November 1, 2002, through November 30, 2011, in 12 villages in southern China. Interventions were implemented starting in 2002 to improve kitchen ventilation (by providing support and instruction for improving biomass stoves or installing exhaust fans) and to promote the use of clean fuels (i.e., biogas) instead of biomass for cooking (by providing support and instruction for installing household biogas digesters); questionnaire interviews and spirometry tests were performed in 2005, 2008, and 2011. That the interventions improved air quality was confirmed via measurements of indoor air pollutants (i.e., SO2, CO, CO2, NO2, and particulate matter with an aerodynamic diameter of 10 µm or less) in a randomly selected subset of the participants' homes. Annual declines in lung function and COPD incidence were compared between those who took up one, both, or neither of the interventions.
Use of clean fuels and improved ventilation were associated with a reduced decline in forced expiratory volume in 1 s (FEV1): decline in FEV1 was reduced by 12 ml/y (95% CI, 4 to 20 ml/y) and 13 ml/y (95% CI, 4 to 23 ml/y) in those who used clean fuels and improved ventilation, respectively, compared to those who took up neither intervention, after adjustment for confounders. The combined improvements of use of clean fuels and improved ventilation had the greatest favorable effects on the decline in FEV1, with a slowing of 16 ml/y (95% CI, 9 to 23 ml/y). The longer the duration of improved fuel use and ventilation, the greater the benefits in slowing the decline of FEV1 (p<0.05). The reduction in the risk of COPD was unequivocal after the fuel and ventilation improvements, with an odds ratio of 0.28 (95% CI, 0.11 to 0.73) for both improvements.
Replacing biomass with biogas for cooking and improving kitchen ventilation are associated with a reduced decline in FEV1 and risk of COPD.
Trial Registration
Chinese Clinical Trial Register ChiCTR-OCH-12002398
Please see later in the article for the Editors' Summary
Editors' Summary
Nearly 3 billion people in developing countries heat their homes and cook by burning biomass—wood, crop waste, and animal dung—in open fires and leaky stoves. Burning biomass this way releases pollutants into the home that impair lung function and that are responsible for more than a million deaths from chronic obstructive pulmonary disease (COPD) every year. COPD is a group of diseases that interfere with breathing. Normally, air is breathed in through the nose or mouth and travels down the windpipe into two bronchial tubes (airways) in the lungs. These tubes branch into smaller tubes (bronchioles) that end in bunches of tiny air sacs (alveoli). Oxygen in the air passes through the thin walls of these sacs into small blood vessels and is taken to the heart for circulation round the body. The two main types of COPD—chronic bronchitis (long-term irritation and swelling of the bronchial tubes) and emphysema (damage to the walls of the alveoli)—make it hard for people to breathe. Most people with COPD have both chronic bronchitis and emphysema, both of which are caused by long-term exposure to cigarette smoke, indoor air pollution, and other lung irritants. Symptoms of COPD include breathlessness during exercise and a persistent cough that produces large amounts of phlegm (mucus). There is no cure for COPD, but drugs and oxygen therapy can relieve its symptoms, and avoiding lung irritants can slow disease progression.
Why Was This Study Done?
Exposure to indoor air pollution has been associated with impaired lung function and COPD in several studies. However, few studies have assessed the long-term effects on lung function and on the incidence of COPD (the proportion of a population that develops COPD each year) of replacing biomass with biogas (a clean fuel produced by bacterial digestion of biodegradable materials) for cooking and heating, or of improving kitchen ventilation during cooking. Here, the researchers undertook a nine-year prospective cohort study in rural southern China to investigate whether these interventions are associated with any effects on lung function and on the incidence of COPD. A prospective cohort study enrolls a group of people, determines their characteristics at baseline, and follows them over time to see whether specific characteristic are associated with specific outcomes.
What Did the Researchers Do and Find?
The researchers offered nearly 1,000 people living in 12 villages in southern China access to biogas and to improved kitchen ventilation. All the participants, who adopted these interventions according to personal preferences, completed a questionnaire about their smoking habits and occupational exposure to pollutants and had their lung function measured using a spirometry test at the start and end of the study. Some participants also completed a questionnaire and had their lung function measured three and six years into the study. Finally, the researchers measured levels of indoor air pollution in a randomly selected subset of homes at the end of the study to confirm that the interventions had reduced indoor air pollution. Compared with non-use, the use of clean fuels and of improved ventilation were both associated with a reduction in the decline in lung function over time after adjusting for known characteristics that affect lung function, such as smoking. The use of both interventions reduced the decline in lung function more markedly than either intervention alone, and the benefits of using the interventions increased with length of use. Notably, the combined use of both interventions reduced the risk of COPD occurrence among the study participants.
What Do These Findings Mean?
These findings suggest that, among people living in rural southern China, the combined interventions of use of biogas instead of biomass and improved kitchen ventilation were associated with a reduced decline in lung function over time and with a reduced risk of COPD. Because participants were not randomly allocated to intervention groups, the people who adopted the interventions may have shared other unknown characteristics (confounders) that affected their lung function (for example, having a healthier lifestyle). Thus, it is not possible to conclude that either intervention actually caused a reduction in the decline in lung function. Nevertheless, these findings suggest that the use of biogas as a substitute for biomass for cooking and heating and improvements in kitchen ventilation might lead to a reduction in the global burden of COPD associated with biomass smoke.
Additional Information
Please access these websites via the online version of this summary at
The US National Heart, Lung, and Blood Institute provides detailed information for the public about COPD
The US Centers for Disease Control and Prevention provides information about COPD and links to other resources (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about COPD, personal stories, and links to other resources
The British Lung Foundation, a not-for-profit organization, provides information about COPD in several languages
The Global Initiative for Chronic Obstructive Lung Disease works to improve prevention and treatment of COPD around the world
The World Health Organization provides information about all aspects of indoor air pollution and health (in English, French, and Spanish)
MedlinePlus provides links to other information about COPD (in English and Spanish)
PMCID: PMC3965383  PMID: 24667834
24.  Control of Breathing During Mechanical Ventilation: Who Is the Boss? 
Respiratory care  2011;56(2):127-139.
Over the past decade, concepts of control of breathing have increasingly moved from being theoretical concepts to “real world” applied science. The purpose of this review is to examine the basics of control of breathing, discuss the bidirectional relationship between control of breathing and mechanical ventilation, and critically assess the application of this knowledge at the patient’s bedside. The principles of control of breathing remain under-represented in the training curriculum of respiratory therapists and pulmonologists, whereas the day-to-day bedside application of the principles of control of breathing continues to suffer from a lack of outcomes-based research in the intensive care unit. In contrast, the bedside application of the principles of control of breathing to ambulatory subjects with sleep-disordered breathing has out-stripped that in critically ill patients. The evolution of newer technologies, faster real-time computing abilities, and miniaturization of ventilator technology can bring the concepts of control of breathing to the bedside and benefit the critically ill patient. However, market forces, lack of scientific data, lack of research funding, and regulatory obstacles need to be surmounted.
PMCID: PMC3116642  PMID: 21333174
artificial respiration; mechanical ventilation; ventilator; obstructive sleep apnea; sleep apnea; servo ventilation; critical illness
25.  Determinants for association and gRNA-directed endonuclease cleavage by purified RNA editing complexes from Trypanosoma brucei 
Journal of molecular biology  2008;381(1):35-48.
U-insertion/deletion RNA editing in the single mitochondrion of ancient kinetoplastids is a unique mRNA maturation process needed for translation. Multi-subunit editing complexes recognize many pre-mRNA sites and modify them via cycles of three catalytic steps: guide-RNA (gRNA) mediated cleavage, insertion or deletion of uridylates at the 3’ terminus of the upstream cleaved piece, and ligation of the two mRNA pieces. While catalytic and many structural protein subunits of these complexes have been identified, the mechanisms and basic determinants of substrate recognition are still poorly understood. The current study defined relatively simple single- and double-stranded determinants for association and gRNA-directed cleavage. To this end, we used an electrophoretic mobility shift assay to directly score the association of purified editing complexes with RNA ligands, in parallel with U.V. photo-crosslinking and functional studies. The cleaved strand required a minimal 5’ overhang of 12-nt and a ~15-bp duplex with gRNA to direct the cleavage site. A second protruding element in either the cleaved or the guide strand was required unless longer duplexes were used. Importantly, the single-stranded RNA requirement for association can be upstream or downstream of the duplex, and the binding and cleavage activities of purified editing complexes could be uncoupled. The current observations together with our previous reports (Cifuentes-Rojas et al., 2005 and 2006) show that association, cleavage and full-round editing by purified editing complexes have distinct determinants that increase in complexity as these editing stages progress. Finally, we found that the endonuclease KREN1 in purified complexes photo-crosslinks with a targeted editing site. A model is proposed whereby one or more RNase III-type endonucleases in editing complexes mediate the initial binding and scrutiny of potential ligands, and subsequent catalytic selectivity triggers either insertion or deletion editing enzymes.
PMCID: PMC2596986  PMID: 18572190

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