Branched germline cysts and female-specific cyst fragmentation facilitate oocyte determination in mice.

During mouse gametogenesis, germ cells derived from the same progenitor are connected via intercellular bridges forming germline cysts, within which asymmetrical or symmetrical cell fate occurs in female and male germ cells, respectively. Here, we have identified branched cyst structures in mice, and investigated their formation and function in oocyte determination. In fetal female cysts, 16.8% of the germ cells are connected by three or four bridges, namely branching germ cells. These germ cells are preferentially protected from cell death and cyst fragmentation and accumulate cytoplasm and organelles from sister germ cells to become primary oocytes. Changes in cyst structure and differential cell volumes among cyst germ cells suggest that cytoplasmic transport in germline cysts is conducted in a directional manner, in which cellular content is first transported locally between peripheral germ cells and further enriched in branching germ cells, a process causing selective germ cell loss in cysts. Cyst fragmentation occurs extensively in female cysts, but not in male cysts. Male cysts in fetal and adult testes have branched cyst structures, without differential cell fates between germ cells. During fetal cyst formation, E-cadherin (E-cad) junctions between germ cells position intercellular bridges to form branched cysts. Disrupted junction formation in E-cad-depleted cysts led to an altered ratio in branched cysts. Germ cell-specific E-cad knockout resulted in reductions in primary oocyte number and oocyte size. These findings shed light on how oocyte fate is determined within mouse germline cysts.

Difficult Intubation due to Penetrating Trauma from a Crossbow Bolt.

We present the case of a patient with penetrating neck and craniofacial trauma from a self-inflicted crossbow bolt injury. This case highlights the challenges involved in prehospital airway management related to an in situ foreign object penetrating the oral cavity. We review the complications associated with such injuries and considerations for effective prehospital airway management.

Assessment of Impulsive and Continuous Low-Frequency Noise in Irish Waters.

As part of the European Union Marine Strategy Framework Directive (MSFD), member states are required to address noise pollution in the marine environment under Descriptor 11. This study aimed to provide a practical desk-based application of Descriptor 11 assessment, focusing on the main contributors of ocean noise pollution in Irish waters, seismic surveying and shipping. To highlight specific geographical areas subject to elevated levels of noise pollution, the proportion of days over a calendar year that seismic air guns were operational was calculated and the vessel density per 50-km(2) grids was determined across Ireland's exclusive economic zone (EEZ). Additionally, cetacean sighting data were used to determine the degree of spatial overlap between areas of elevated noise pollution and areas of cetacean abundance.

The Use of Deep Water Berths and the Effect of Noise on Bottlenose Dolphins in the Shannon Estuary cSAC.

The Shannon Estuary on the west coast of Ireland is one of Europe's premier deepwater berths catering for ships up to 200,000 deadweight tonnage. It is also Ireland's only designated candidate special area of conservation for bottlenose dolphins under the EU Habitats Directive. Long-term static acoustic monitoring was carried out at a number of intensive shipping sites. In 2012, noise monitoring took place over a 6-month period (at 1 site) as part of Ireland's requirements under the Marine Strategy Framework Directive (MSFD). This is the first assessment of the potential effect of vessel traffic on the behavior of this discrete dolphin population.

Case-control study of hepatitis B and hepatitis C in older adults: Do healthcare exposures contribute to burden of new infections?

UNLABELLED: Reports of hepatitis B virus (HBV) and hepatitis C virus (HCV) transmission associated with unsafe medical practices have been increasing in the United States. However, the contribution of healthcare exposures to the burden of new infections is poorly understood outside of recognized outbreaks. We conducted a case-control study at three health departments that perform enhanced viral hepatitis surveillance in New York and Oregon. Reported cases of symptomatic acute hepatitis B and hepatitis C occurring in persons≥55 years of age from 2006 to 2008 were enrolled. Controls were identified using telephone directories and matched to individual cases by age group (55-59, 60-69, and ≥70 years) and residential postal code. Data collection covered exposures within 6 months before symptom onset (cases) or date of interview (controls). Forty-eight (37 hepatitis B and 11 hepatitis C) case and 159 control patients were enrolled. Case patients were more likely than controls to report one or more behavioral risk exposures, including sexual or household contact with an HBV or HCV patient, >1 sex partner, illicit drug use, or incarceration (21% of cases versus 4% of controls exposed; matched odds ratio [mOR]=7.1; 95% confidence interval [CI]: 2.1, 24.1). Case patients were more likely than controls to report hemodialysis (8% of cases; mOR=13.0; 95% CI: 1.5, 115), injections in a healthcare setting (58%; mOR=2.7; 95% CI: 1.3, 5.3), and surgery (33%; mOR=2.3; 95% CI: 1.1, 4.7). In a multivariate model, behavioral risks (adjusted OR [aOR]=5.4; 95% CI: 1.5, 19.0; 17% attributable risk), injections (aOR=2.7; 95% CI: 1.3, 5.8; 37% attributable risk), and hemodialysis (aOR=11.5; 95% CI: 1.2, 107; 8% attributable risk) were associated with case status. CONCLUSION: Healthcare exposures may represent an important source of new HBV and HCV infections among older adults.

Lupus dermal fibroblasts are proinflammatory and exhibit a profibrotic phenotype in scarring skin disease.

Fibroblasts are stromal cells known to regulate local immune responses important for wound healing and scar formation; however, the cellular mechanisms driving damage and scarring in patients with cutaneous lupus erythematosus (CLE) remain poorly understood. Dermal fibroblasts in patients with systemic lupus erythematosus (SLE) experience increased cytokine signaling in vivo, but the effect of inflammatory mediators on fibroblast responses in nonscarring versus scarring CLE subtypes is unclear. Here, we examined responses to cytokines in dermal fibroblasts from nonlesional skin of 22 patients with SLE and CLE and 34 individuals acting as healthy controls. Notably, inflammatory cytokine responses were exaggerated in SLE fibroblasts compared with those from individuals acting as healthy controls. In lesional CLE biopsies, these same inflammatory profiles were reflected in single-cell RNA-Seq of SFRP2+ and inflammatory fibroblast subsets, and TGF-ß was identified as a critical upstream regulator for inflammatory fibroblasts in scarring discoid lupus lesions. In vitro cytokine stimulation of nonlesional fibroblasts from patients who scar from CLE identified an upregulation of collagens, particularly in response to TGF-ß, whereas inflammatory pathways were more prominent in nonscarring patients. Our study revealed that SLE fibroblasts are poised to hyperrespond to inflammation, with differential responses among patients with scarring versus nonscarring disease, providing a potential skin-specific target for mitigating damage.

Effects of positive airway pressure therapy on neurobehavioral outcomes in children with obstructive sleep apnea.

RATIONALE: Positive airway pressure therapy is frequently used to treat obstructive sleep apnea in children. However, it is not known whether positive airway pressure therapy results in improvements in the neurobehavioral abnormalities associated with childhood sleep apnea. OBJECTIVES: We hypothesized that positive airway pressure therapy would be associated with improvements in attention, sleepiness, behavior, and quality of life, and that changes would be associated with therapy adherence. METHODS: Neurobehavioral assessments were performed at baseline and after 3 months of positive airway pressure therapy in a heterogeneous group of 52 children and adolescents. MEASUREMENTS AND MAIN RESULTS: Adherence varied widely (mean use, 170 ± 145 [SD] minutes per night). Positive airway pressure therapy was associated with significant improvements in attention deficits (P < 0.001); sleepiness on the Epworth Sleepiness Scale (P < 0.001); behavior (P < 0.001); and caregiver- (P = 0.005) and child- (P < 0.001) reported quality of life. There was a significant correlation between the decrease in Epworth Sleepiness Scale at 3 months and adherence (r = 0.411; P = 0.006), but not between other behavioral outcomes and adherence. Behavioral factors also improved in the subset of children with developmental delays. CONCLUSIONS: These results indicate that, despite suboptimal adherence use, there was significant improvement in neurobehavioral function in children after 3 months of positive airway pressure therapy, even in developmentally delayed children. The implications for improved family, social, and school function are substantial. Clinical trial registered with www.clinicaltrials.gov (NCT 00458406).

Clinical utility of repeated positive airway pressure titrations in children with obstructive sleep apnea syndrome.

STUDY OBJECTIVES: Positive airway pressure (PAP) is the second line of treatment for obstructive sleep apnea syndrome in children. It is common practice following initiation of PAP to perform repeat titration polysomnography to re-evaluate the patient's therapeutic pressure; however, data supporting this practice are lacking. We hypothesized that repeat PAP titration would result in significant setting changes in children with obstructive sleep apnea syndrome. METHODS: We retrospectively analyzed demographic, polysomnographic, and PAP data of children with obstructive sleep apnea syndrome aged 0-18 years who were initiated on PAP and underwent 2 titration studies over a 2-year period. PAP mode and recommended pressure differences between the 2 titrations were compared. RESULTS: 64 children met inclusion criteria. The median (interquartile range) baseline obstructive apnea-hypopnea index and SpO2 nadir were 14.8 (8.7-32.7) events/h and 88.5% (85-92%), respectively. The mean differences in obstructive apnea-hypopnea index, SpO2 nadir, and % total sleep time with SpO2 < 90% between both titrations were negligible, including children with obesity, adenotonsillar hypertrophy, and trisomy 21. Additionally, there was no significant difference in mean PAP pressure between 2 separate titration studies for those on continuous PAP or bilevel PAP. CONCLUSIONS: Overall, repeat PAP titration in children with obstructive sleep apnea syndrome within the timeframe here described did not result in significant changes in PAP mode, continuous PAP pressure, or obstructive apnea-hypopnea index. Based on these data, repeat PAP titration within 2 years of an initial titration does not appear to be necessary. CITATION: Yendur O, Feld L, Miranda-Schaeubinger M, et al. Clinical utility of repeated positive airway pressure titrations in children with obstructive sleep apnea syndrome. J Clin Sleep Med. 2022;18(4):1021-1026.

Continuous positive airway pressure care for pediatric obstructive sleep apnea: A long-term quality improvement initiative.

Successful treatment of pediatric obstructive sleep apnea syndrome (OSAS) with continuous positive airway pressure (CPAP) is challenging due to behavioral, technical, medical, and systems factors. We undertook a quality improvement (QI) initiative involving physicians, nurses, psychologists, and respiratory therapists to improve CPAP outpatient care and processes. We aimed to: (1) increase the proportion of patients with a follow-up visit within 4 months of initiation of CPAP, (2) reduce the median time to first follow-up visit to under 4 months, and (3) increase the proportion of patients obtaining a post-initiation polysomnogram within 1 year to >50%. We also explored healthcare utilization (HCU) in a subsample of patients. Interventions focused on developing a tracking system and standardizing interdisciplinary clinical care. The proportion of patients returning to clinic within 4 months improved from 38.2% to 65.5% and median time to first follow-up visit improved from 133 to 56 days. The percentage of patients who returned for a post-initiation polysomnogram within 1 year was 71.1%. Subsample analyses showed significant reductions in the length of stay for emergency department visits from pre-CPAP initiation (Mdn = 3.00 h; interquartile range [IQR] = 7.00) to post-initiation (Mdn = 2.00 h, IQR = 5.00). The length of hospitalizations was also significantly shorter from pre (Mdn = 48.00 h, IQR = 243.00) to post-CPAP initiation (Mdn = 0.00 h, IQR = 73.00). A standardized, tracked approach to interdisciplinary outpatient CPAP care can improve follow-up care and potentially HCU.

SARS-CoV-2 infection results in immune responses in the respiratory tract and peripheral blood that suggest mechanisms of disease severity.

Respiratory tract infection with SARS-CoV-2 results in varying immunopathology underlying COVID-19. We examine cellular, humoral and cytokine responses covering 382 immune components in longitudinal blood and respiratory samples from hospitalized COVID-19 patients. SARS-CoV-2-specific IgM, IgG, IgA are detected in respiratory tract and blood, however, receptor-binding domain (RBD)-specific IgM and IgG seroconversion is enhanced in respiratory specimens. SARS-CoV-2 neutralization activity in respiratory samples correlates with RBD-specific IgM and IgG levels. Cytokines/chemokines vary between respiratory samples and plasma, indicating that inflammation should be assessed in respiratory specimens to understand immunopathology. IFN-α2 and IL-12p70 in endotracheal aspirate and neutralization in sputum negatively correlate with duration of hospital stay. Diverse immune subsets are detected in respiratory samples, dominated by neutrophils. Importantly, dexamethasone treatment does not affect humoral responses in blood of COVID-19 patients. Our study unveils differential immune responses between respiratory samples and blood, and shows how drug therapy affects immune responses during COVID-19.

Positive Airway Pressure for the Treatment of OSA in Infants.

BACKGROUND: Positive airway pressure (PAP) is a standard therapy for the treatment of OSA in children, but objective data on the effectiveness of PAP in infants are sparse. The aim of this study was to compare the effectiveness of PAP in infants younger than 6 months of age with that in school-aged children. RESEARCH QUESTION: Compared with PAP in school-aged children, can PAP be titrated as successfully in infants, and is adherence to PAP similar in both age groups? STUDY DESIGN AND METHODS: Single-center retrospective study. For consecutive infants younger than 6 months of age and school-aged children 5 to 10 years of age with OSA treated with PAP, baseline and titration polysomnography data, PAP adherence data, and parent-reported barriers to adherence were compared between groups. RESULTS: Forty-one infants and 109 school-aged children were included. Median obstructive apnea hypopnea index (OAHI) in infants was 25.7/h (interquartile range [IQR], 17.8-35.9/h) and was greater than that in school-aged children (12.1/hr; IQR, 7.6-21.5/h; P < .0001). After PAP titration, OAHI was reduced by a median of 92.1% in infants, similar to the median 93.4% reduction in school-aged children (P = .67). PAP was used in infants on 94.7% of nights, which was more than the 83% in school-aged children (P = .003). No differences were found in barriers to adherence between infants and school-aged children, with behavioral barriers being most common in both groups. INTERPRETATION: Objective data demonstrate that PAP is both highly effective at treating OSA and well-tolerated in infants. Like older patients, PAP should be considered along with other therapies for the treatment of OSA in even the youngest children.

Auto-titrating CPAP for the treatment of obstructive sleep apnea in children.

STUDY OBJECTIVES: In-laboratory titration polysomnography (PSG) is standard to determine optimal therapeutic continuous positive airway pressure (CPAP) in children with obstructive sleep apnea (OSA). The use of auto-titrating CPAP devices (autoCPAP) as an alternative to CPAP titration has not been well studied in children. We hypothesized that autoCPAP-derived pressures (PMEAN, PPEAKMEAN, P90) would be similar to titration PSG pressure (PPSG). METHODS: This is a retrospective study of children with OSAS initiated on autoCPAP between 2007 and 2017, who used autoCPAP for at least 2 h/night and who had adequate titration PSG were included in the analysis. AutoCPAP-derived pressures were obtained from use downloads and compared with PPSG. PPSG predictive factors were analyzed by median regression. Nonparametric methods were used for analysis. RESULTS: Of 110 children initiated on autoCPAP, 44 satisfied the inclusion criteria. Age (median (interquartile range)) was 13.01 (9.98-16.72) years, and 63.6% were obese. PPSG median (interquartile range) was 8 (7-11) cmH2O, mean autoCPAP-derived pressure (PMEAN) was 6.2 (5.6-7.6) cmH2O, peak mean pressure (PPEAKMEAN) was 9.4 (7.7-11.1) cmH2O, and average device pressure ≤ 90% of the time (P90) was 8.1 (7.2-9.7) cmH2O. AutoCPAP-derived pressures correlated with PPSG (P < .05). PMEAN was lower than the other 3 pressures (P < .0002). Median regression analysis demonstrated that after adjusting for patient characteristics such as age, sex, and obesity status, autoCPAP-derived pressures remained significant predictors of PPSG (P < .05). There were no significant interactions between these patient characteristics and autoCPAP-derived pressures. CONCLUSIONS: This study demonstrates that autoCPAP-derived pressures correlate with the titration PSG-derived pressures. These results indicate that autoCPAP can be used in the pediatric population and can determine pressures that are close to the titration pressures.

The role of polysomnography in tracheostomy decannulation of children with bronchopulmonary dysplasia.

BACKGROUND: Patients with bronchopulmonary dysplasia (BPD) may require tracheostomy for long-term mechanical ventilation. Polysomnography (PSG) may predict successful decannulation in children, however it is unclear how this success compares with children without a PSG. To better evaluate this role, we compared decannulation outcomes between tracheostomy-dependent children with BPD who underwent PSG before decannulation to those who did not. METHODS: This is a retrospective cohort study between 1 January 2007 and 1 June 2017 of tracheostomy-dependent children with BPD who were clinically considered for decannulation. Patient demographics, PSG results, and medical comorbidities were abstracted from medical records and compared between groups. Decannulation outcomes were compared between children with BPD who underwent PSG before decannulation and those who did not. RESULTS: One hundred twenty-five patients with BPD were considered for tracheostomy decannulation. Forty-six (37%) had a pre-decannulation PSG while 79 (63%) did not. Nineteen (41%) patients did not undergo decannulation within 6 months of the PSG. One (3%) patient with pre-decannulation PSG failed decannulation. Four (5%) patients without pre-decannulation PSG failed decannulation. Nineteen patients with PSG and no decannulation had significantly higher obstructive apnea-hypopnea index (OAHI) (13.62 vs 2.68 events per hour, P = 0.004), higher end-tidal CO 2 max (52.84 vs 48.03 mm Hg, P = 0.035), and were older at PSG (median age, 6.04 vs 4.04 years, P = 0.008). CONCLUSIONS: While successful decannulation can be achieved without a PSG in some patients, PSG is a valuable tool to identify BPD patients undergoing clinical evaluation for decannulation who would benefit from treatment of OSA before decannulation.

Adherence to Positive Airway Pressure for the Treatment of Obstructive Sleep Apnea in Children With Developmental Disabilities.

STUDY OBJECTIVES: To determine whether adherence to positive airway pressure (PAP) differs in children with developmental disabilities (DD) compared to typically developing (TD) children. METHODS: PAP adherence of 240 children initiated on PAP for obstructive sleep apnea (OSA) was retrospectively analyzed. Adherence between groups, expressed as percentage of nights used and hours of usage on nights used at 3 and 6 months, was compared. Predictive factors of adherence were studied using a median regression model. RESULTS: A total of 103 children with DD (median [interquartile range] age = 7.9 [3.2-13.1] years) and 137 TD (11.0 [5.5-16.1], P = .005) children were included. Percentage of nights used was significantly higher in children with DD at 3 (DD = 86.7 [33.9-97.9], TD = 62.9 [30.8-87.8] P = .01) and 6 months (DD = 90.0 [53.3-100], TD = 70.7 [29.2-90.8], P = .003). Hours of usage on nights used at 3 and 6 months were similar between groups (DD = 5.0 [1.4-7.9], TD = 4.6 [1.9-7.2], P = .715; DD = 6.4 [1.8-8.3], TD = 5.7 [2.5-7.3], P = .345, respectively). This adherence measure improved over time in both groups (DD, P = .007; TD, P = .005). At 6 months, higher median neighborhood income and titration at or before 6 months were significantly predictive for percentage of nights used; higher PAP pressure was significantly predictive for hours of usage in both groups. CONCLUSIONS: Children with DD had better PAP adherence expressed as percentage of nights used than TD children. Hours of usage on nights used at 3 and 6 months were similar between groups and improved over time. Higher income and titration at or before 6 months were predictive of adherence in all children. These findings indicate that children with DD can successfully wear PAP.

Financial Analysis of an Intensive Pediatric Continuous Positive Airway Pressure Program.

Study Objectives: Continuous positive airway pressure (CPAP) is effective in treating obstructive sleep apnea in children, but adherence to therapy is low. Our center created an intensive program that aimed to improve adherence. Our objective was to estimate the program's efficacy, cost, revenue and break-even point in a generalizable manner relative to a standard approach. Methods: The intensive program included device consignment, behavioral psychology counseling, and follow-up telephone calls. Economic modeling considered the costs, revenue and break-even point. Costs were derived from national salary reports and the Pediatric Health Information System. The 2015 Medicare reimbursement schedule provided revenue estimates. Results: Prior to the intensive CPAP program, only 67.6% of 244 patients initially prescribed CPAP appeared for follow-up visits and only 38.1% had titration polysomnograms. In contrast, 81.4% of 275 patients in the intensive program appeared for follow-up visits (p < .001) and 83.6% had titration polysomnograms (p < .001). Medicare reimbursement levels would be insufficient to cover the estimated costs of the intensive program; break-even points would need to be 1.29-2.08 times higher to cover the costs. Conclusions: An intensive CPAP program leads to substantially higher follow-up and CPAP titration rates, but costs are higher. While affordable at our institution due to the local payer mix and revenue, Medicare reimbursement levels would not cover estimated costs. This study highlights the need for enhanced funding for pediatric CPAP programs, due to the special needs of this population and the long-term health risks of suboptimally treated obstructive sleep apnea.

Pulmonary capillaritis with hemorrhage due to propylthiouracil therapy in a child.

We report on a case of pulmonary capillaritis with diffuse alveolar hemorrhage in a child due to propylthiouracil (PTU). PTU treatment is a rare cause of pulmonary capillaritis in adults; we report on the first case in a pediatric patient. The treatment of pulmonary capillaritis often requires corticosteroid therapy, other immunosuppressive medications, or withdrawal of the causative agent. Our patient recovered completely after treatment with a limited course of corticosteroids and removal of PTU.

Phase I trial of intranasal and endobronchial administration of a recombinant adeno-associated virus serotype 2 (rAAV2)-CFTR vector in adult cystic fibrosis patients: a two-part clinical study.

Recombinant adeno-associated serotype 2-based vectors (rAAV2) possess a number of theoretical advantages for cystic fibrosis (CF) gene therapy because they elicit little or no inflammatory response and generally result in stable expression. rAAV2 vectors expressing the cystic fibrosis transmembrane conductance regulator (CFTR) gene have previously been shown to mediate stable correction of the CF defect in CF bronchial epithelial cells and stable expression of CFTR in rabbit and nonhuman primate models. Here we report the results of the first trial initiated with rAAV in humans, a phase I study in 25 adult and adolescent CF patients with mild to moderate lung disease. Doses of the rAAV-CFTR vector (tgAAVCF) ranging from 3 x 10(1) to 1 x 10(9) replication units (RU), which is equivalent to approximately 6 x 10(4) to 2 x 10(12) DNase resistant particles (DRP), were administered to one side of the nose and to the superior segment of the lower lobe of the right lung. Several adverse events were noted prior to and/or after vector delivery, but most of them appeared to be related to the endogenous CF lung disease or a result of the bronchoscopic procedures. Only one of the serious events was judged to be possibly vector-related (based on temporal association), and this event was a pulmonary exacerbation very similar to several others experienced by the same subject in the three months preceding vector delivery. Vector shedding was minimal throughout the study, and serum-neutralizing antibodies were detected after vector delivery to subjects in the highest dosage cohorts. Gene transfer as measured by DNA polymerase chain reaction (PCR) was not observed until cohort 10 in nasal and bronchial epithelia. Sporadic low-level copy numbers suggested gene transfer of anywhere from 0.002 copies per cell up to 0.5 copies per cell was possible; however, DNA PCR was positive in lungs prior to direct dosing suggesting aspiration from the nasal dosing. These data indicate the need for continued evaluation of rAAV-CFTR vectors in additional clinical trials.

Problematic variation in local institutional review of a multicenter genetic epidemiology study.

CONTEXT: Sequencing of the human genome provides an immense resource for studies correlating DNA variation and epidemiology. However, appropriately powered genetic epidemiology studies often require recruitment from multiple sites. OBJECTIVES: To document the burden imposed by review of multicenter studies and to determine the variability among local institutional review boards (IRBs) in the approval of a multicenter genetic epidemiology study. DESIGN: A PubMed search was performed to determine the frequency of citations of multicenter studies by 5-year intervals from 1974 through 2002. A 7-question survey was sent to all participating study centers to obtain information on frequency of IRB meetings, dates for submission and approval, use/nonuse of a specific consent form, type of review performed, types of consent forms required, preparation time, and number of changes requested by the IRB at each center. Centers also provided a copy of all consent forms they generated and IRB correspondence regarding the study. SETTING AND PARTICIPANTS: Thirty-one of 42 cystic fibrosis care centers in this single US multicenter genetic epidemiology study of cystic fibrosis replied, yielding a 74% response rate. MAIN OUTCOME MEASURES: Frequency of published research studies and consistency among IRBs. RESULTS: The number of all published single-center studies has increased 1.3-fold since 1985, while the number of published epidemiology and genetic epidemiology multicenter studies increased by 8- and 9-fold, respectively, during this same period. Evaluation of the risk of the same genetic epidemiology study by 31 IRBs ranged from minimal to high, resulting in 7 expedited reviews (23%) and 24 full reviews (77%). The number of consents required by the IRBs ranged from 1 to 4; 15 IRBs (48%) required 2 or more consents, while 10 (32%) did not require assent for children. The most common concern (52%) of IRBs pertained to the genetic aspects of the study. CONCLUSIONS: Review of a protocol for a multicenter genetic epidemiology study by local IRBs was highly variable. Lack of uniformity in the review process creates uneven human subjects protection and incurs considerable inefficiency. The need for reform, such as the proposed centralized review, is underscored by the ever increasing rate of genetic discoveries facilitated by the Human Genome Project and the unprecedented opportunity to assess the relevance of genetic variation to public health.

Sleep Patterns in Children with Cystic Fibrosis.

This study examined sleep patterns and the association between sleep and perceived health for children with and without CF. Ninety families (45 CF) completed questionnaires about the child's sleep and health. Significant group differences were found for sleep patterns (bedtime, wake time, total sleep time), symptoms of sleep disordered breathing, and sleep disturbances. Poorer perceived health was associated with sleep disturbances among children with CF, but not for children without CF. This study highlights the importance of including sleep in the evaluation of children with CF, as both medical and behavioral interventions can improve the sleep of children with CF.