National Audit of Criteria For Pre-Operative Sickle Cell Screening in Children.

Aim We set out to identify the current practice in the anaesthesiology departments of Ireland's public hospitals that deliver paediatric anaesthesia with regard to pre-operative screening for sickle cell disease (SCD) and Sickle cell trait (SCT). Methods The Departments of Anaesthesiology at 14 public HSE-funded hospitals that deliver paediatric anaesthesia were contacted over a three month period in 2020. Any existing policies regarding pre-operative screening of paediatric patients for Sickle cell disease or trait were sought. Comparisons were made between any screening policies in place. Results A response was received from 11 of the 14 hospitals. Three out of 11 of the Anaesthesiology Departments have formal policies in place. The ethnicities identified for pre-operative screening varied across these three hospitals. Conclusion Despite a significant increase in the number of people of African, middle Eastern & Indian descent living in Ireland in recent years, no neonatal screening programme for Sickle cell exists here, and no national policy exists with criteria to guide the practice of pre-operative screening of patients for SCD/SCT (trait). Our survey highlights a lack of standardisation in the approach to pre-operative sickle cell screening of children across Ireland's public hospital system. In view of the increasing multiculturalism in Ireland we recommend a national review of the merits of the introduction of developing a targeted national guideline for pre-operative screening for sickle cell in at-risk children.

Electromagnetic torque measurements in DIII-D using internal/external magnetic field decomposition.

Given spatially resolved measurements of normal and tangential components of the magnetic field just outside the surface of a magnetically confined plasma, the field at the measurement location can be uniquely decomposed into contributions from the plasma and from external sources. This principle allows direct measurement of the electromagnetic torque on the plasma without knowledge of the distribution of the internal and external currents, similar to the more well-known formalism using the Maxwell stress tensor. The internal/external field decomposition also enables a mixed approach that incorporates any explicitly known current distributions (e.g., from non-axisymmetric coils). We discuss the requirements and limitations of such an approach to torque measurements. Experimental measurements of the torque evolution as a rotating tearing mode locks to the wall in the DIII-D tokamak are consistent with a simple model.

Methods to determine the radiated power in SPI-mitigated disruptions in JET.

This paper presents techniques for evaluating the radiated power in JET disruptions. Disrupting plasmas are shown to have non-axisymmetric radiation profiles, motivating the re-evaluation of the standard techniques for calculating the total radiated power at JET using bolometry. Four single-channel bolometers at different toroidal locations are exploited to quantify the radiation asymmetry. Toroidal radiation peaking factors integrated over the entire disruption of up to 1.5 have been observed when varying the quantity of neon in pellets used in disruptions mitigated by shattered pellet injection. Using synthetic bolometer diagnostics developed with the Cherab spectroscopy modeling framework, we can estimate the systematic error on total power calculations for relevant radiation profiles and improve estimates of the total radiated power. We show that the component of the systematic error on the total power due to the poloidal radiation profile can be reduced from 70% to 10% with suitable assumptions about the structure of the poloidal profile.

A Strategy for Wellness in a Pathology Residency Program: Enhancing Chances of Success During an Epidemic of Burnout.

Physician burnout is a national crisis with medicine among occupations with higher suicide risk, at 1.8 times the national average. Few pathology departments address this issue, and even fewer residency programs offer formal resiliency training. We implemented a high-stress environment resiliency strategy and an Accreditation Council for Graduate Medical Education-compliant curriculum to our residency program. Its purpose was to apply initiatives employed in the finance industry, then to measure their effectiveness. Utilizing methods from financial companies such as Goldman Sachs, we adopted the following initiatives in our residency program: (1) approach burnout as a dilemma requiring a tridimensional strategy: providing wellness training for the individual, programmatic group strategies, and an institutional wellness plan; (2) formalize a wellness curriculum, implementing wellness talks focused on stress prevention, management, and treatment; (3) offer free sessions with resilience coaches, psychological help, Employee Assistance Program, and chaplain services; (4) modify our mentorship program, pairing first-year residents with senior residents; (5) implement mindfulness practices; (6) provide easy access to volunteer opportunities and networking; (7) offer fitness center discounts. Effectiveness was measured through 2 surveys of 13 residents representing day 0 (before wellness initiatives were implemented) and at 1 year. Results indicate a significant improvement in utilization of wellness tools. This study demonstrates that wellness and resilience can be taught. Our ultimate goals are to increase wellness among pathology residents, to prepare them for a high-stress environment before entering the workforce, and to prepare them to incorporate the tools they have learned into their new workplaces.

How would Mary Poppins fare in labour? Practically perfect? Unlikely.

Introduction Unrealistic expectations of labour in first time mothers can present challenges to physicians and midwives. This study calculated the percentage of "practically perfect" births in nulliparous women, defined as a labour without intervention, an intact perineum and a positive neonatal outcome. Methods: This was a retrospective study of the nulliparous deliveries that occurred in the National Maternity Hospital over two years (2014/2015). To extract the perfect births, we excluded deliveries <37 weeks, induction/pre labour Caesarean Section (CS), Artificial Rupture of Membranes (ARM), oxytocin, fetal blood sample, emergency CS/instrumental deliveries, perineal damage and suboptimal Apgar scores. Results: 0.8% of nulliparous mothers had a practically perfect birth. Discussion Our results provide a useful statistic for clinicians and nulliparous mothers, which could be further validated by similar studies in similar units. The study had a large cohort which objectively quantified perfect births. Research on the subjective perception of perfect births could add value to these findings.

Economic evaluations of system-based obesity interventions - the case for a new approach.

System-based interventions are of increasing interest as they seek to modify environments (e.g. socio-cultural system, transport system or policy system) that promote development of conditions such as obesity and its related risk factors. In our commentary, we draw attention to features of the system-based approach that may explain the relative absence of economic evaluations of the cost-effectiveness of these interventions, needed to guide decision-making on which to deploy. We present and discuss potentially applicable methods and alternative approaches based on our experiences in two major system-based interventions currently underway (in Melbourne, Australia and Gaggenau, Germany) that begin to fill this gap. We feel the issues and potential solutions outlined in this commentary are important for a broad range of stakeholders (e.g. clinicians, interventionalists, policy makers) to consider as they seek to address the issue of obesity.

Prediction of Packed Cell Volume after Whole Blood Transfusion in Small Ruminants and South American Camelids: 80 Cases (2006-2016).

BACKGROUND: Calculation of desired whole blood transfusion volume relies on an estimate of an animal's circulating blood volume, generally accepted to be 0.08 L/kg or 8% of the animal's body weight in kilograms. OBJECTIVE: To use packed cell volume before and after whole blood transfusion to evaluate the accuracy of a commonly used equation to predict packed cell volume after transfusion in small ruminants and South American camelids; to determine the nature and frequency of adverse transfusion reactions in small ruminants and camelids after whole blood transfusion. ANIMALS: Fifty-eight small ruminants and 22 alpacas that received whole blood transfusions for anemia. METHODS: Retrospective case series; medical record review for small ruminants and camelids that received whole blood transfusions during hospitalization. RESULTS: Mean volume of distribution of blood as a fraction of body weight in sheep (0.075 L/kg, 7.5% BW) and goats (0.076 L/kg, 7.6% BW) differed significantly (P < 0.01) from alpacas (0.103 L/kg, 10.3% BW). Mild transfusion reactions were noted in 16% of transfusions. CONCLUSIONS AND CLINICAL RELEVANCE: The generally accepted value of 8% for circulating blood volume (volume of distribution of blood) is adequate for calculation of transfusion volumes; however, use of the species-specific circulating blood volume can improve calculation of transfusion volume to predict and achieve desired packed cell volume. The incidence of transfusion reactions in small ruminants and camelids is low.

Longitudinal relationship between fecal culture, fecal quantitative PCR, and milk ELISA in Mycobacterium avium ssp. paratuberculosis-infected cows from low-prevalence dairy herds.

Mycobacterium avium ssp. paratuberculosis (MAP), the causative agent of ruminant Johne's disease, presents a particular challenge with regard to infection mitigation on dairy farms. Diagnostic testing strategies to identify and quantify MAP and associated antibodies are imperfect, and certain facets of the relationship between diagnostic tests remain to be explored. Additional repeated-measures data from known infected animals are needed to complement the body of cross-sectional research on Johne's disease-testing methods. Statistical models that accurately account for multiple diagnostic results while adjusting for the effects of individual animals and herds over time can provide a more detailed understanding of the interplay between diagnostic outcomes. Further, test results may be considered as continuous wherever possible so as to avoid the information loss associated with dichotomization. To achieve a broader understanding of the relationship between diagnostic tests, we collected a large number of repeated fecal and milk samples from 14 infected cows, in addition to bulk milk samples, from 2 low-prevalence dairy herds in the northeast United States. Predominately through the use of mixed linear modeling, we identified strong associations between milk ELISA optical density, fecal quantitative PCR, and fecal culture in individual animals while concurrently adjusting for variables that could alter these relationships. Notably, we uncovered subtleties in the predictive abilities of fecal shedding level on milk ELISA results, with animals categorized as disease progressors reaching higher ELISA optical density levels. Moreover, we observed that spikes in fecal shedding could predict subsequent high ELISA values up to 2 mo later. We also investigated the presence of MAP in individual milk samples via PCR and noted an association between poor udder hygiene and MAP positivity in milk, suggesting some level of environmental contamination. The paucity of positive milk samples and the complete absence of detectable MAP in the bulk tank throughout the study period indicate that contamination of milk with MAP may not be of chief concern in low-prevalence herds. An enhanced understanding of the interrelationships between diagnostic tests can only benefit the development of testing strategies and objectives, which in turn may lessen MAP infection prevalence in dairy herds.

Plasma Peak and Trough Gentamicin Concentrations in Hospitalized Horses Receiving Intravenously Administered Gentamicin.

BACKGROUND: Gentamicin is an aminoglycoside antimicrobial commonly used in horses at 6.6 mg/kg IV once daily. Therapeutic drug monitoring (TDM) can confirm desired peak concentration is reached for common bacterial isolates, and detect toxicosis associated with high trough values. OBJECTIVES: Determine the relationship between gentamicin dose and plasma concentration in hospitalized horses, and identify a starting dose range to achieve peaks > 32 µg/mL. ANIMALS: Sixty-five horses (2002-2010) receiving once-daily gentamicin with TDM performed (N = 99 sets). METHODS: Retrospective study. Data from hospitalized horses including weight, dose, plasma peak, and trough gentamicin concentration, creatinine concentrations and presence of focal or systemic disease were collected from medical records. Peak concentrations measured 25-35 minutes after administration were included (N = 77). Data were divided into low (<7.7 mg/kg), medium (7.7-9.7 mg/kg) and high (>9.7 mg/kg) dose groups, and were grouped by the horse having focal or systemic disease. RESULTS: Peak concentrations resulting from doses ≥7.7 mg/kg were 5.74 µg/mL (SE 2.1 µg/mL) greater than peaks from doses <7.7 mg/kg (P = .007). Peak concentrations was 3.6 times more likely to be >32 µg/mL if dose was ≥7.7 mg/kg (P = .04). There were no significant effects of dose on trough or creatinine concentration. At a given dose, horses with focal disease had higher peaks than those with systemic disease (P = .039). CONCLUSIONS AND CLINICAL IMPORTANCE: These data suggest gentamicin dosage should be individually determined in horses using TDM, but support an initial once-daily dose of 7.7-9.7 mg/kg IV to achieve peaks >32 µg/mL and trough concentrations <2 µg/mL. Further studies evaluating the safety of doses >6.6 mg/kg are required.

Gastrointestinal ultrasonography of normal Standardbred neonates and frequency of asymptomatic intussusceptions.

BACKGROUND: Ultrasonographic appearance of the gastrointestinal (GI) tract of equine neonates has not been completely described. OBJECTIVES: To describe (1) sonographic characteristics of the GI segments in normal nonsedated equine neonates, (2) intra- and interobserver variation in wall thickness, and (3) the sonographic appearance of asymptomatic intussusceptions, and (4) to compare age and sonographic findings of foals with and without asymptomatic intussusceptions. ANIMALS: Eighteen healthy Standardbred foals ≤5 days of age. METHODS: Prospective, cross-sectional blinded study. Gastrointestinal sonograms were performed stall-side. Intraobserver variability in wall thickness measurements was determined by calculating the coefficient of variation (CV). The Bland-Altman method was used to assess interobserver bias. Student's t-test and Fisher's exact test were used to test the association among presence of intussusceptions, age, and selected sonographic findings. RESULTS: The reference ranges (95% predictive interval) for wall thickness were 1.6-3.6 mm for the stomach, 1.9-3.2 mm for the duodenum, 1.9-3.1 mm for the jejunum, 1.3-2.2 mm for the colon, and 0.8-2.7 mm for the cecum. Intraobserver wall thickness CV ranged from 8 to 21% for the 2 observers for 5 gastrointestinal segments. The interobserver bias for wall thickness measurements was not significant except for the stomach (0.14 mm, P < .05) and duodenum (0.29 mm, P < .05). Diagnostic images of mural blood flow could not be obtained. Asymptomatic intussusceptions were found in 10/18 neonates. Associations between sonographic variables or age and the presence of intussusceptions were not found. CONCLUSIONS AND CLINICAL IMPORTANCE: Sonographic characteristics of the GI tract of normal Standardbred neonates can be useful in evaluating ill foals. Asymptomatic small intestinal intussusceptions occur in normal Standardbred neonates.

Prevalence of Mycobacterium avium subsp. paratuberculosis fecal shedding in alpacas presented to veterinary hospitals in the United States.

BACKGROUND: The prevalence of Johne's disease in alpacas in the United States is unknown. The limits of polymerase chain reaction (PCR) detection of Mycobacterium avium subsp. paratuberculosis (MAP) in alpaca feces have not been determined. OBJECTIVES: To evaluate the use of PCR for MAP detection in alpaca feces; and to estimate the prevalence of MAP fecal shedding in alpacas presented to veterinary teaching hospitals. ANIMALS: Alpacas presenting to 4 US veterinary teaching hospitals from November 2009 to February 2011. METHODS: Prospective study. Ten dilutions of a wild MAP strain were added to negative alpaca feces and processed for MAP detection by means of a commercial real-time PCR (RT-PCR) assay, and cultured on Herrold's Egg Yolk Medium (HEYM) and liquid broth. The limits of detection for each method were determined. Fecal samples from alpacas admitted to the veterinary teaching hospitals during the study period were evaluated for MAP via PCR and HEYM. RESULTS: The lowest MAP dilution detectable via PCR was 243 MAP colony-forming units (CFU)/g of feces, at which concentration MAP growth was detectable on HEYM. Ten (6%; 95% confidence interval: 3-9%) of the 180 fecal samples collected were positive on PCR. CONCLUSIONS AND CLINICAL IMPORTANCE: Polymerase chain reaction can provide an accurate and rapid detection of MAP fecal shedding in alpacas; and the prevalence of MAP fecal shedding in hospitalized alpacas in 4 US veterinary teaching hospitals was 6%.

Indirect fluorescent antibody test and surface antigen ELISAs for antemortem diagnosis of equine protozoal myeloencephalitis.

BACKGROUND: Recent research suggests that serum : CSF titer ratios could provide the most accurate antemortem diagnosis of equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona. OBJECTIVES: The purpose of this study was to assess the utility of two commercially available tests, the indirect fluorescent antibody test (IFAT) and the surface antigen 2, 4/3 ELISA (SAG2, 4/3 ELISA), using archived paired serum and CSF samples. ANIMALS: Samples were obtained from 4 types of clinical patients. Confirmed positive cases (n = 9 horses; 11 sample sets) had neurologic deficits and postmortem lesions consistent with EPM. Confirmed negative cases (n = 28) had variable clinical signs and postmortem lesions consistent with another disease. Suspected positive cases (n = 6) had neurologic deficits consistent with EPM, marked improvement after treatment, and exclusion of other diseases. Suspected negative cases (n = 14) had variable signs with a strong presumptive diagnosis of another disease. METHODS: For each test, descriptive statistics were calculated using serum results alone, CSF results alone, and a serum : CSF titer ratio. RESULTS: Overall accuracy was highest for SAG2, 4/3 ELISA titer ratio at 0.97 (95% CI 0.88-0.99) with sensitivity = 0.88 (95% CI 0.66-0.97) and specificity = 1 (95% CI 0.92-1). IFAT CSF and titer ratio results also showed high accuracy at 0.88 (95% CI 0.77-0.94), but lower sensitivity = 0.65 (95% CI 0.41-0.83). CONCLUSIONS AND CLINICAL IMPORTANCE: Using serum results alone was least accurate for both test types. The more accurate methods, such as the SAG2, 4/3 ELISA serum : CSF titer ratio, should be utilized.

Patients with recurrent glioblastoma multiforme. Initial experience with p-[(131)I]iodo-L-phenylalanine and external beam radiation therapy.

AIM: The objective of this study was to assess the feasibility, dosimetry, tolerability and efficacy of systemically administrated p-[(131)I]iodo-L-phenylalanine ((131)IPA) combined with hypo-fractionated external beam radiation therapy (EBRT) in patients with recurrent glioblastoma multiforme (GBM). PATIENTS, METHODS: Five patients (2 women, 3 men, aged 27-69) with recurrent GBM and exhaustion of regular therapy options were included. All had a positive O-(2-[(18)F]Fluoroethyl)-L-tyrosine positron emission tomography (FET-PET) and pretherapeutic dosimetry was performed. Tumour targeting was verified by (131)IPA-SPECT up to six days after radiotracer administration. After (131)IPA therapy, patients were treated with hypo-fractionated EBRT in six fractions of 5 Gy (n = 4) or in eleven fractions of 2 Gy in one case. RESULTS: Based on the individual dosimetry, the patients received a single intravenous administration of 2 to 7 GBq of (131)IPA, resulting in radiation absorbed doses to the blood of 0.80-1.47 Gy. The treatment was well tolerated; only minor complaints of nausea and vomiting that responded to ondansetron and pantoprazol were noticed in the first two patients. After preventive medication, the last three patients had no complaints during therapy. In none of the patients a decrease of leukocyte or thrombocyte counts below the baseline level or the lower normal limit was observed. Tumour doses from (131)IPA were low (≤ 1 Gy) and all patients died three to eight (median 5.5) months after therapy. CONCLUSION: In this initial experience, treatment of GBM with (131)IPA in combination with EBRT was demonstrated to be safe and well tolerated, but less effective than suggested by the animal studies.

Paratuberculosis (Johne's disease) in cattle and other susceptible species.

Paratuberculosis (Johne's disease) is a widespread and costly disease. This consensus statement will summarize recommendations regarding diagnosis, control, and treatment of Johne's disease in cattle and other species. Each section of recommendations is followed by a statement that subjectively characterizes the strength of the supporting evidence. The role played by Mycobacterium avium subsp. paratuberculosis (MAP) in the pathogenesis has been a matter of controversy for many years. This statement concludes with an assessment of the evidence in favor of MAP as a potential zoonotic pathogen.

Comparison of preoperative short-course radiotherapy and long-course radiochemotherapy for locally advanced rectal cancer.

BACKGROUND: The purpose of this work was to perform a single institution comparison between preoperative short-course radiotherapy (SC-RT) and long-course radiochemotherapy (LC-RCHT) for locally advanced rectal cancer. METHODS: A total of 225 patients with clinical stage UICC II-III rectal cancer were treated with SC-RT (29 Gy in 10 twice daily fractions followed by immediate surgery; n = 108) or LC-RCHT (54 Gy in 28 fractions with simultaneous 5-fluorouracil (5-FU) ± oxaliplatin chemotherapy followed by delayed surgery; n = 117). All patients in the LC-RCHT cohort and patients in the SC-RT with pathological UICC stage ≥ II received adjuvant chemotherapy. Before 2004, the standard of care was SC-RT with LC-RCHT reserved for patients where downstaging was considered as required for sphincter preservation or curative resection. In the later period, SC-RT was practiced only for patients unfit for radiochemotherapy. RESULTS: Patients in the LC-RCHT cohort had a significantly higher proportion of cT4 tumors, clinical node positivity, and lower tumor location. The 5-year local control (LC) and overall survival (OS) were 91% and 66% without differences between the SC-RT and LC-RCHT groups. Acute toxicity was increased during LC-RCHT (grade ≥ II 1% vs. 33%) and there were no differences in postoperative complications. Severe late toxicity grade ≥ III was increased after SC-RT (12% vs. 3%). Of patients aged > 80 years, 7 of 7 patients and 4 of 9 patients received curative surgery after SC-RT and LC-RCHT, respectively. CONCLUSION: Despite the fact that patients with worse prognostic factors were treated with LC-RCHT, there were no significant differences in LC and OS between the SC-RT and LC-RCHT group. Age > 80 years was identified as a significant risk factor for LC-RCHT and these patients could be treated preferably with SC-RT.

Metabolic activation of sulfur mustard leads to oxygen free radical formation.

We recently published electron paramagnetic resonance (EPR) spin trapping results that demonstrated the enzymatic reduction of sulfur mustard sulfonium ions to carbon-based free radicals using an in vitro system containing sulfur mustard, cytochrome P450 reductase, NADPH, and the spin trap α-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) in buffer (A.A. Brimfield et al., 2009, Toxicol. Appl. Pharmacol. 234:128-134). Carbon-based radicals have been shown to reduce molecular oxygen to form superoxide and, subsequently, peroxyl and hydroxyl radicals. In some cases, such as with the herbicide paraquat, a cyclic redox system results, leading to magnified oxygen free radical concentration and sustained tissue damage. Low mustard carbon radical concentrations recorded by EPR in our in vitro system, despite a robust (4.0mM) sulfur mustard starting concentration, led us to believe a similar oxygen reduction and redox cycling process might be involved with sulfur mustard. A comparison of the rate of mustard radical-POBN adduct formation in our in vitro system by EPR at atmospheric and reduced oxygen levels indicated a sixfold increase in 4-POBN adduct formation (0.5 to 3.0 µM) at the reduced oxygen concentration. That result suggested competition between oxygen and POBN for the available carbon-based mustard radicals. In parallel experiments we found that the oxygen radical-specific spin trap 5-tert-butoxycarbonyl-5-methylpyrroline-N-oxide (BMPO) detected peroxyl and hydroxyl radicals directly when it was used in place of POBN in the in vitro system. Presumably these radicals originated from O(2) reduced by carbon-based mustard radicals. We also showed that reactive oxygen species (ROS)-BMPO EPR signals were reduced or eliminated when mustard carbon radical production was impeded by systematically removing system components, indicating that carbon radicals were a necessary precursor to ROS production. ROS EPR signals were completely eliminated when superoxide dismutase and catalase were included in the complete in vitro enzymatic system, providing additional proof of oxygen radical participation. The redox cycling hypothesis was supported by density functional theory calculations and frontier molecular orbital analysis.

Antimicrobial activity of gallium nitrate against Mycobacterium avium subsp. paratuberculosis in neonatal calves.

BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP), the agent of Johne's disease in cattle, is a facultative intracellular bacterium that is dependent on ferric iron for its survival and replication. Gallium (Ga), a trivalent semimetal that shares many similarities with ferric iron and functions as an iron mimic has been shown to have in vitro antimicrobial activity against several microorganisms, including MAP. OBJECTIVES: (1) To investigate the antimicrobial activity of Ga in calves experimentally infected with MAP; and (2) to monitor for potential adverse effects of Ga on calf health. ANIMALS: Twelve Holstein calves. METHODS: Randomized blind controlled experiment. Beginning at 10 days of age (study day 1), the experimental calves (n = 6) were treated with 20 mg/kg gallium nitrate daily for 45 days. On study days 4 and 5, all calves were challenged with a PO dose of a live field strain MAP. Treated calves were monitored daily for adverse effects. Calves were euthanized on study day 100, and 29 tissue samples and 1 fecal sample were collected from each calf. Samples were cultured for MAP by MGIT liquid culture system, Herrold's Egg Yolk Medium culture, or both. RESULTS: No adverse effects were observed in the treated calves. Treatment was associated with a significant reduction in MAP tissue burden when compared with control calves (P = .017). CONCLUSIONS AND CLINICAL RELEVANCE: Chemoprophylactic treatment of calves with Ga before and during the period of high susceptibility decreased MAP tissue colonization in experimentally infected neonatal calves.

Nasal potential difference to detect Na+ channel dysfunction in acute lung injury.

Pulmonary fluid clearance is regulated by the active transport of Na(+) and Cl(-) through respiratory epithelial ion channels. Ion channel dysfunction contributes to the pathogenesis of various pulmonary fluid disorders including high-altitude pulmonary edema (HAPE) and neonatal respiratory distress syndrome (RDS). Nasal potential difference (NPD) measurement allows an in vivo investigation of the functionality of these channels. This technique has been used for the diagnosis of cystic fibrosis, the archetypal respiratory ion channel disorder, for over a quarter of a century. NPD measurements in HAPE and RDS suggest constitutive and acquired dysfunction of respiratory epithelial Na(+) channels. Acute lung injury (ALI) is characterized by pulmonary edema due to alveolar epithelial-interstitial-endothelial injury. NPD measurement may enable identification of critically ill ALI patients with a susceptible phenotype of dysfunctional respiratory Na(+) channels and allow targeted therapy toward Na(+) channel function.