Cystic fibrosis screening, evaluation, and management of hepatobiliary disease consensus recommendations.

Cystic fibrosis (CF) may cause a spectrum of hepatobiliary complications, including portal hypertension, multilobular cirrhosis, and liver failure. Current guidelines on the detection and monitoring of hepatobiliary complications in CF were published in 1999. The CF Foundation assembled a committee to evaluate research advances and formulate revised guidelines for CF-associated liver disease. A committee of hepatologists, gastroenterologists, pulmonologists, pharmacists, nurses, dietitians, individuals with CF, and the parents of a child with CF devised "population, intervention, comparison, and outcome" questions regarding hepatobiliary disease in CF. PubMed literature searches were performed for each population, intervention, comparison, and outcome question. Recommendations were voted on with 80% agreement required to approve a recommendation. Public comment on initial recommendations was solicited prior to the formulation of final recommendations. Thirty-one population, intervention, comparison, and outcome questions were assembled, 6401 manuscripts were title screened for relevance, with 1053 manuscripts undergoing detailed full-text review. Seven recommendations were approved for screening, 13 for monitoring of existing disease, and 14 for treatment of CF-associated hepatobiliary involvement or advanced liver disease. One recommendation on liver biopsy did not meet the 80% threshold. One recommendation on screening ultrasound was revised and re-voted on. Through a multidisciplinary committee and public engagement, we have assembled updated recommendations and guidance on screening, monitoring, and treatment of CF-associated hepatobiliary involvement and advanced liver disease. While research gaps remain, we anticipate that these recommendations will lead to improvements in CF outcomes through earlier detection and increased evidence-based approaches to monitoring and treatment.

A national clinician survey on the British Society for Dermatological Surgery guidelines on antithrombotic agent use in skin surgery.

Antithrombotic medication is taken by 14-22% patients undergoing skin surgery, with more patients now taking direct oral anticoagulants (DOACs). The latest evidence suggests that the risk of stopping DOACs perioperatively is low in skin surgery, particularly for primary closures, but remains unclear for more complex procedures. The 2016 British Society for Dermatological Surgery (BSDS) guidelines suggest that clinicians could consider stopping DOACs in patients for 24-48 h, based on individual bleeding risk. We surveyed BSDS members to better understand clinical practice and guideline adherence with a view to updating the guidance. The results demonstrated that there is consistency among clinicians in the management of patients on more established antithrombotic agents, such as aspirin, clopidogrel and warfarin. However, there is a higher perceived risk of significant haematomas following higher-risk procedures such as larger flaps or grafts with DOACs vs. other antithrombotics postoperatively. Stopping DOACs perioperatively for 24-48 h for higher-risk procedures can be cautiously considered following an individual risk assessment and informed discussion with the patient.

The potential to manage releases of Bacillus anthracis using bioretention and a high flow media filter: Results of simulated runoff testing with tracer spores Bacillus globigii.

The threat of bioterrorism has spurred research on the decontamination and containment of different agents. Anthrax [causative agent Bacillus anthracis (Ba)] is a disease that can lead to severe infections within human and animals, particularly when inhaled. This research investigated the use of spore-contaminated simulated runoff events into stormwater control measures (SCMs), which are designed to retain and improve the quality of runoff and may have the potential to filter and contain the spores. In this study, the effectiveness of a bioretention cell (BRC) and high flow media filter (HFMF) in Huron, Ohio, were evaluated for removal of Bacillus globigii (Bg) spores (a harmless cognate of Ba). Three 4-8 mm simulated runoff events were created for each SCM using a fire hydrant and Bg spores were injected into the runoff upstream of the SCM inlets. The BRC significantly (p < 0.001) outperformed the HFMF in reducing Bg concentrations and loads, with an average load reduction of 1.9 log (∼99% reduction) compared to 0.4 (∼60% reduction), respectively. A probable critical design factor leading to these differences was the infiltration rate of the media and subsequent retention time within the filters, which was supported by similar disparities in suspended solids reductions. Differences in spore removal may also have been due to particle size distribution of the HFMF, which was more gravelly than the bioretention cell. At 3 and 6 months after the-simulated runoff tests, soil samples taken from both SCMs, yielding detectable Bg spores within the top 15 cm of media, with increased spore concentrations where ponding occurred for longer durations during the tests. This suggests that forebays and areas near inlets may be hotspots for spore cleanup in a real-world bioterrorism incident.

Pulmonary Function and Quality of Life in Adults with Cystic Fibrosis.

PURPOSE: People living with cystic fibrosis (CF) experience impaired quality of life, but the extent to which pulmonary function is associated with quality of life in CF remains unclear METHODS: Using baseline data from a trial of specialist palliative care in adults with CF, we examined the association between pulmonary obstruction and quality of life (measured with the Functional Assessment of Chronic Illness Therapy Total Score). RESULTS: Among 262 participants, median age was 33, and 78% were on modulator therapy. The median quality of life score was higher in those with mild obstruction (135, IQR 110-156) compared to moderate (125, IQR 109-146) and severe obstruction (120, IQR 106-136). In an unadjusted model, we observed a non-significant trend toward lower quality of life with increased obstruction-compared to participants with mild obstruction, those with moderate obstruction had quality of life score 7.46 points lower (95% CI -15.03 to 0.10) and those with severe obstruction had a score 9.98 points lower (95% CI -21.76 to 1.80). However, this association was no longer statistically significant in the adjusted model, which may reflect confounding due to sex, age, BMI, and modulator therapy. Comorbidities (depression and anxiety) and social determinants of health (financial insecurity and education) were also associated with quality of life. CONCLUSION: Advancing our understanding of patient-centered markers of quality of life, rather than focusing on pulmonary function alone, may help identify novel interventions to improve quality of life in this patient population.

An international survey characterizing Mohs tissue processing techniques and Mohs margin thresholds: how close is too close?

BACKGROUND: From practice, we identified heterogeneity in Mohs micrographic surgery (MMS) specimen tissue processing techniques and specifications, and in the Mohs surgeons' assessment of MMS specimen histological tumour clearance. AIM: By surveying an international cohort of Mohs surgeons, we determined to characterize variation in margin threshold assessment (number of wafers/sections free of tumour to declare tumour clearance). METHODS: An online questionnaire was distributed to Mohs surgeons in the UK, European countries, Australia and New Zealand, assessing the background demographics of the surgeons and the technical factors involved in MMS tissue processing and posing three MMS scenarios to define margin thresholds. RESULTS: In total, 114 consultant/attending-level Mohs surgeons responded, giving a response rate of 33.5% from 20 countries (including UK nations). The first scenario posed was a 20-mm cheek basal cell carcinoma (BCC) excised by MMS with a fully complete first wafer (7 µm) clear of tumour and the second wafer (after trimming interval of 50 µm) demonstrating a small dermal focus of nodular BCC; of the 58 surgeons, 16 (27.6%) would not take another stage. With a follow-up question, 16 of the 58 (27.6%) surgeons specified wanting three clear sections to declare tumour clearance. When the same scenario had a change to a 20-mm infiltrative BCC, 84.2% (48 of 57 surgeons) required a second MMS stage, with a follow-up question clarifying that a third (19 of 57) wanted three clear sections to determine clearance. For a well-differentiated 15-mm squamous cell carcinoma with the same factors there was no majority consensus, with the same proportion of surgeons (22.6%; 12 of 53) calling tumour clearance after one, two and three clear section(s) respectively. For MMS specimen processing specifications, routine sections/wafers of 5-10 µm were reported by 77.4% of respondents (48 of 62) and for trimming interval values, 78.6% (48 of 61) specified a range between 20 and 200 µm. CONCLUSION: By surveying international Mohs surgeons, we highlight surgeon background characteristics, peer-compare assessment of margin thresholds for tumour clearance across three scenarios, and delineate tissue processing and intraoperative approaches.

A review of Mohs micrographic surgery for skin cancer. Part 3: Squamous cell carcinoma.

This review presents and discusses the evidence for MMS to treat cutaneous squamous cell carcinoma (cSCC). The MEDLINE, Embase and Cochrane databases were searched; 39 papers were identified for recurrence and 2 papers for cost-effectiveness. We included all clinical trials and observational studies, including retrospective reports, and excluded editorials and systematic reviews or meta-analyses. We categorized the evidence under the following headings: tumour recurrence, specific site outcomes (ear, lip, scalp and periocular), cSCC with perineural invasion, and cost-effectiveness. Although there are many observational studies indicating the potential benefits of MMS in the management of certain cSCCs, no randomized controlled trials (RCT) were identified. The evidence from comparitor studies suggests that MMS has a lower recurrence rate than that of other treatments for cSCC, including standard excision. Many studies identified were single-armed, but did demonstrate a low to very low recurrence rate of cSCC following MMS. A single recent study suggests MMS for intermediate cSCC is highly cost-effective compared with wide local excision when all-in costs are considered. Since the overall quality of included studies was mixed and highly heterogeneous, further methodologically robust studies with comparator arms or comprehensive long-term registry data would be valuable. It would be ideal to employ a definitive multicentre RCT but given the evidence to date and multiple advantages to MMS, the lack of clinical equipoise makes this difficult to justify. Comparison with current modalities would likely not be ethical/achievable on a like-for-like basis given MMS provides 100% margin assessment, enables histological clearance prior to reconstruction, and minimizes the removal of uninvolved tissue.

A review of the evidence for Mohs micrographic surgery. Part 2: basal cell carcinoma.

Mohs micrographic surgery (MMS) is considered the gold-standard treatment for basal cell carcinoma (BCC) particularly for sites with a high-risk of incomplete excision such as the central face, for tumours with an aggressive growth pattern and consequent unpredictable subclinical extension and for recurrent tumours. However, the process is more time-consuming than for standard excision (SE), and the magnitude of benefit is uncertain. This article aims to provide a more complete picture of current evidence, including a review of cosmetic outcomes, tissue-sparing ability and cost-effectiveness of MMS. Although robust evidence is lacking, there is a large volume of observational data supporting a low recurrence rate after MMS. The risk of incomplete excision and higher recurrence rate of standard excision favours the use of MMS at high-risk sites. There is some low-certainty evidence that MMS results in a smaller defect size compared with SE, and that incomplete excision with SE results in larger defects. Larger defects may affect cosmetic outcome but there is no direct evidence that MMS improves cosmetic outcome compared with SE. There is conflicting evidence regarding the cost of MMS compared with SE, as some studies consider MMS less expensive than SE and others consider it more expensive, which may reflect the healthcare setting. A multicentre 10-year randomized controlled trial comparing MMS and SE in the treatment of high-risk BCC would be desirable, but is unlikely to be feasible or ethical. Collection of robust registry data capturing both MMS and SE outcomes would provide additional long-term outcomes.

A multinational survey characterizing the use of surgical magnifying loupes in dermatological surgery.

BACKGROUND: The use of surgical loupes has not been well-documented in dermatological surgery. OBJECTIVES: An online questionnaire was developed to characterize the use of loupes in dermatological surgery. METHODS: The questionnaire was circulated to the memberships of the British Society of Dermatological Surgery, the European Society of Micrographic Surgery, and the Australasian College of Dermatologists. Responses were analyzed with a mixed methods approach using quantitative data analysis and inductive content analysis. RESULTS: One-hundred twenty-five valid responses were received from 20 nations. Most respondents were from England (40%; 50/125), Australia (16%; 20/125), and the Netherlands (14.4%; 18/125). Overall, 71.2% (89/125) of respondents were consultants/Facharzt/attending. Furthermore, 55.2% (69/125) of respondents were Mohs surgeons. In dermatological surgery 38.4% (48/125) of respondents used surgical loupes routinely. The mode magnification level for loupes was 2.5× (67.5%; 27/40), with 3× second place (12.5%; 5/40). Exactly half (20/40) used through-the-lens style loupes and 40% (16/40) used flip-up-loupes. Inductive content analysis of the 51 free-text responses from nonloupe users uncovered several deterring factor themes, including expense (18/51), can manage without/don't need (14/51), and narrow field of view a(11/51), and uncomfortable/too heavy (9/51). CONCLUSIONS: This is the first time the use of surgical loupes in dermatological surgery has been internationally characterized.

Formal vs. informal transition in adolescents with cystic fibrosis: A retrospective comparison of outcomes.

BACKGROUND: The aim of this study was to survey young adults who participated in either a formal or semi-formal transition program at one cystic fibrosis (CF) care center to compare their self-perceived transition related anxiety, transition readiness and satisfaction with transition teaching and timing. METHODS: This retrospective cohort study was conducted from 3/1/2015 to 9/30/2016. Study participants met inclusion criteria if they had a diagnosis of CF, received pediatric care from the care center, transitioned to adult care between 1/1/2009 and 3/1/2016 and had at least six months experience in adult care. Participants completed a 43 question Likert-type survey rating their pre-transfer transition related anxiety, transition readiness, and satisfaction with the transition preparation and process. FINDINGS: Participation in a structured transition program was associated with decreased anxiety at transition time (p < .05), increased transition readiness (p < .01) and increased self-perceived healthcare independence (p < .01). Only 48% of participants were satisfied with their chosen transition time, with 18% wishing they had moved to adult care sooner and 34% wishing they could have delayed their transfer to adult care longer. DISCUSSION: This study supports that participation in a formalized transition program was associated with significantly lower pre-transfer anxiety and higher post-transition satisfaction in individuals with CF. Age at transfer initiation was not associated with satisfaction or perceived readiness to transfer. PRACTICE IMPLICATIONS: Disease-specific knowledge acquisition in transition curriculum does not necessarily correlate to task-completion skills. Teams should partner with young adults to choose the right transition time.

Next generation swale design for stormwater runoff treatment: A comprehensive approach.

Swales are the oldest and most common stormwater control measure for conveying and treating roadway runoff worldwide. Swales are also gaining popularity as part of stormwater treatment trains and as crucial elements in green infrastructure to build more resilient cities. To achieve higher pollutant reductions, swale alternatives with engineered media (bioswales) and wetland conditions (wet swales) are being tested. However, the available swale design guidance is primarily focused on hydraulic conveyance, overlooking their function as an important water quality treatment tool. The objective of this article is to provide science-based swale design guidance for treating targeted pollutants in stormwater runoff. This guidance is underpinned by a literature review. The results of this review suggest that well-maintained grass swales with check dams or infiltration swales are the best options for runoff volume reduction and removal of sediment and heavy metals. For nitrogen removal, wet swales are the most effective swale alternative. Bioswales are best for phosphorus and bacteria removal; both wet swales and bioswales can also treat heavy metals. Selection of a swale type depends on the site constraints, local climate, and available funding for design, construction, and operation. Appropriate siting, pre-design site investigations, and consideration of future maintenance during design are critical to successful long-term swale performance. Swale design recommendations based on a synthesis of the available research are provided, but actual design standards should be developed using local empirical data. Future research is necessary to identify optimal design parameters for all swale types, especially for wet swales.

Survey of the operational status of twenty-six urban stormwater biofilter facilities in Sweden.

This study evaluates the operational status of twenty-six biofilter facilities across nine cities in Sweden, with respect to their functional design criteria, engineered design features (filter media composition, hydraulic conductivity, and drawdown time), and includes a visual inspection of the biofilter components (pre-treatment, in/outlet structures, filter media, and vegetation). These indicators were used to examine the performance level of each biofilter in achieving their design objectives set by the operators. Furthermore, it was investigated whether the biofilter facilities had been properly maintained to meet the objectives. Results indicate that the soil media used was consistent with respect to percentage sand, fines, and organic matter and comparable to design recommendations used by municipalities in other countries. The field-tested hydraulic conductivity for the biofilters ranged from 30 to 962 mm/h. This range of values, along with noticeable sediment accumulation within the biofilter indicate that not all the sites were operating optimally. Pre-treatment stages in poor condition with high volumes of sediment and litter accumulation were the primary causes for, and indicators of, low hydraulic conductivity rates. The ponding volume calculations revealed that at least 40 % of facilities did not have enough capacity to retain every-day and/or design rainfall due to design and/or construction flaws. These analyses raise concerns that, for a considerable number of the biofilters surveyed, water retention and flood protection identified by operators as prioritised objectives are not being met. This raises significant concerns about the functionality of biofilter in practice. Finally, some suggestions are given for tackling the design and maintenance problems discovered.

Hydrologic and water quality performance of two aging and unmaintained dry detention basins receiving highway stormwater runoff.

Dry detention basins (DDBs) are a type of stormwater control measure (SCM) designed to provide flood storage, peak discharge reduction, and some water quality improvement through sedimentation. DDBs are ubiquitous in the urban environment, but are expensive to maintain. In this study, two overgrown DDBs near Raleigh, NC, receiving highway runoff were monitored for up to one year to quantify their water quality and hydrologic performance. Both basins, B1 and B2, have not received vegetation maintenance since construction in 2007. Flow-weighted composite samples were collected during storm events and analyzed for nutrients (Total Phosphorus (TP), Ortho-phosphorus (OP), Ammonia-N (NH3), NO2-3-N (NOX), and Total Kjeldahl Nitrogen (TKN)), total suspended solids (TSS), and total Cd, Cu, Pb, and Zn. An annual water balance was also conducted to quantify runoff volume reduction. Despite low influent concentrations from the highway, significant removal efficiencies were found for all constituents except NH3 in B1. TP, OP, NOX, TSS, and Zn were reduced in B2. Both basins achieved greater than 41% volume reduction through soil infiltration and evapotranspiration, resulting in significant pollutant load reductions for all detected constituents, between 59% and 79% in B1 and 35% and 81% in B2. This study provides evidence that overgrown and unmaintained DDBs can reduce pollutant concentrations comparable to those reported for maintained DDBs, while reducing more volume than standard DDBs. Moreover, carbon sequestration likely increases while maintenance costs decrease.

Insights from using in-situ ultraviolet-visible spectroscopy to assess nitrogen treatment and subsurface dynamics in a regenerative stormwater conveyance (RSC) system.

Regenerative stormwater conveyance (RSC) is a recently developed stormwater control measure that marries the concepts of bioretention and stream restoration. RSC mitigates stormwater runoff by converting surface flow to subsurface seepage using a series of pools and riffles built over a sand media bed. Subsurface seepage flows through media and exits the RSC beneath the outlet weir. Previous studies on RSC pollutant mitigation have focused on surface flow discharges from the RSC. To date, no known research has been conducted on the potential pollutant contributions of RSC seepage, despite the fact that this water also enters receiving waters. This research used Multi-Point Sampling coupled with in-situ ultraviolet-visual spectroscopy to measure nitrogen in seepage during simulated storm events (n = 9) at a field-scale RSC in Raleigh, North Carolina. Calibrations between light absorbance and concentrations were acceptable (Nash-Sutcliffe coefficient > 0.65) for nitrate and total ammoniacal nitrogen (TAN) and very good (Nash-Sutcliffe coefficient > 0.90) for total Kjehdahl nitrogen (TKN). Early storm simulations revealed some initial nutrient flushing from the substrate, which subsided by the third simulation. Overall, subsurface seepage nitrate, TAN, and TKN concentrations were lower by 29%, 57%, and 4% relative to storm inflow concentrations, respectively. Computed subsurface nitrogen concentrations demonstrated temporal variability, highlighting dynamic transport and biogeochemical transformations in saturated and unsaturated conditions. Nitrogen concentrations were lower in seepage than in surface flow; however, due to the high volume of runoff converted to seepage, nitrogen loads discharged in seepage can be larger than those of surface flow. Further research is needed to examine subsurface pollutant reductions under varying hydrologic and seasonal conditions.

Evaluation of Australian dermatological postoperative patient information leaflets: Should we have a national checklist?

BACKGROUND/OBJECTIVES: Patient information leaflets (PILs) are frequently provided to patients following dermatological surgery to provide advice and reassurance in the community. This evaluation reviewed the guidance specified in postoperative PILs across the 40 Australian dermatology teaching departments and clinics. METHODS: All 40 departments and clinics were identified and asked to provide their postoperative information leaflets on sutured wound care (preferable) or excision biopsy (September-October 2015). For each PIL, 10 preselected parameters were evaluated. RESULTS: In total, 28/40 (70%) of units responded. From these units, 11/28 (39.3%) stated they do not use a postoperative PIL. Of the 17 units that provided PILs, the mode minimum dressing duration was 24 (6/17; 35.3%) and 48 h (6/17; 35.3%). For haemostatic advice, 12 PILs specified the time to press on a bleeding wound, with the most common advice being 10 (3/12; 25%) and 20 min (3/12; 25%). Of the 14 PILs that provided analgesic advice, the mode information suggested using paracetamol only and avoiding aspirin (4/14, 28.6%). Two or more signs of infection were stated in 11/17 (64.7%) PILs; 7/17 (41.2%) advised applying petroleum jelly to the wound, almost all PILs highlighted the contact for postoperative problems 16/17 (94.1%), and 5/17 (29.4%) leaflets mentioned scarring. Altogether 8/17 (47.1%) of PILs advised on the timeframe until active exercise could resume postoperatively. CONCLUSION: Guidance provided in Australian postoperative dermatological PILs is heterogeneous. A consensus checklist or template would be beneficial and ensure that advice provided to patients is more consistent; this could be adapted for local factors.

Hydrologic and water quality performance of permeable pavement with internal water storage over a clay soil in Durham, North Carolina.

Permeable pavement is an effective tool for improving stormwater hydrology and water quality when sited over soils with high infiltration rates, but its efficacy over less permeable soils is uncertain. This study examined permeable pavement performance when built over a low-conductivity, clay soil. Four parking stalls (50 m2 total area) were retrofitted with permeable interlocking concrete pavement (PICP) to treat 15.2 m2 of contributing impervious area (0.3:1 run-on ratio). Using an elevated underdrain, the site incorporated a 150-mm internal water storage (IWS) zone to increase exfiltration and promote anaerobic conditions for denitrification. From March 2014-April 2015, 22% of influent runoff volume was reduced via exfiltration and evaporation. Inter-event drawdown of the IWS zone created storage to capture and exfiltrate more than 70% of the runoff volume from precipitation events less than 8 mm, and peak flows were significantly reduced (median 84%). Relative to stormwater runoff from a nearby impermeable asphalt reference watershed, the permeable pavement produced significantly lower event mean concentrations (EMCs) of all pollutants except nitrate, which was significantly higher. Permeable pavement effluent and reference watershed runoff were 99%, 68%, and 96% different for total suspended solids (TSS), total nitrogen (TN), and total phosphorus (TP), respectively. Significantly lower permeable pavement effluent EMCs for copper (Cu, 79%), lead (Pb, 92%) and zinc (Zn, 88%) were also observed. The median effluent concentrations of TN (0.52 mg/L), TP (0.02 mg/L), and TSS (7 mg/L) were all very low relative to the literature. Sampling of nitrogen species in the IWS zone 12, 36, 60, and 84 h post-rainfall was done to better understand mechanisms of nitrogen removal in permeable pavement; results indicated denitrification may be occurring in the IWS zone. Effluent pollutant load from the permeable pavement was at minimum 85% less than from nearby untreated asphalt runoff for TP, TSS, Cu, Pb, and Zn, and was 73% less for TN. Permeable pavements built over low-permeability soils with internal water storage can considerably improve long-term hydrology and water quality.

Stormwater management in nutrient-sensitive watersheds: a case study investigating impervious cover limits and pollutant-load regulations.

The objective of this research project was to compare two stormwater management strategies within a nutrient-sensitive watershed: impervious cover limits versus pollutant-load regulations. A case study was conducted in the nutrient-sensitive Falls Lake watershed in North Carolina, USA, where a commercial fitness complex was constructed in a zone previously restricted to low-density housing. The Falls Lake watershed has a stormwater regulation that limits total nitrogen and total phosphorus export loads to 2.47 kg/ha/yr and 0.37 kg/ha/yr, respectively. Hydrology and water quality were monitored pre- and post-development to quantify changes to stormwater volumes, pollutant concentrations, and annual export loading rates. On-site stormwater control measures (SCMs) reduced nutrient export loading rates below the regulatory standard. However, increased stormwater volumes and nutrient export loading rates were observed from pervious surfaces that were disturbed during construction (total nitrogen increased from 2.06 to 4.24 kg/ha/yr, total phosphorus increased from 0.41 to 0.73 kg/ha/yr). Results from this case study suggest that (1) impervious cover limits do not adequately account for a parcel's nutrient export loads and (2) SCMs that reduce volume and treat pollutants can reduce nutrient export loads below regulatory levels in the Falls Lake watershed.

Universal Features in Phonological Neighbor Networks.

Human speech perception involves transforming a countinuous acoustic signal into discrete linguistically meaningful units (phonemes) while simultaneously causing a listener to activate words that are similar to the spoken utterance and to each other. The Neighborhood Activation Model posits that phonological neighbors (two forms [words] that differ by one phoneme) compete significantly for recognition as a spoken word is heard. This definition of phonological similarity can be extended to an entire corpus of forms to produce a phonological neighbor network (PNN). We study PNNs for five languages: English, Spanish, French, Dutch, and German. Consistent with previous work, we find that the PNNs share a consistent set of topological features. Using an approach that generates random lexicons with increasing levels of phonological realism, we show that even random forms with minimal relationship to any real language, combined with only the empirical distribution of language-specific phonological form lengths, are sufficient to produce the topological properties observed in the real language PNNs. The resulting pseudo-PNNs are insensitive to the level of lingustic realism in the random lexicons but quite sensitive to the shape of the form length distribution. We therefore conclude that "universal" features seen across multiple languages are really string universals, not language universals, and arise primarily due to limitations in the kinds of networks generated by the one-step neighbor definition. Taken together, our results indicate that caution is warranted when linking the dynamics of human spoken word recognition to the topological properties of PNNs, and that the investigation of alternative similarity metrics for phonological forms should be a priority.

Insulin signaling via the PI3-kinase/Akt pathway regulates airway glucose uptake and barrier function in a CFTR-dependent manner.

Cystic fibrosis-related diabetes is the most common comorbidity associated with cystic fibrosis (CF) and correlates with increased rates of lung function decline. Because glucose is a nutrient present in the airways of patients with bacterial airway infections and because insulin controls glucose metabolism, the effect of insulin on CF airway epithelia was investigated to determine the role of insulin receptors and glucose transport in regulating glucose availability in the airway. The response to insulin by human airway epithelial cells was characterized by quantitative PCR, immunoblot, immunofluorescence, and glucose uptake assays. Phosphatidylinositol 3-kinase/protein kinase B (Akt) signaling and cystic fibrosis transmembrane conductance regulator (CFTR) activity were analyzed by pharmacological and immunoblot assays. We found that normal human primary airway epithelial cells expressed glucose transporter 4 and that application of insulin stimulated cytochalasin B-inhibitable glucose uptake, consistent with a requirement for glucose transporter translocation. Application of insulin to normal primary human airway epithelial cells promoted airway barrier function as demonstrated by increased transepithelial electrical resistance and decreased paracellular flux of small molecules. This provides the first demonstration that airway cells express insulin-regulated glucose transporters that act in concert with tight junctions to form an airway glucose barrier. However, insulin failed to increase glucose uptake or decrease paracellular flux of small molecules in human airway epithelia expressing F508del-CFTR. Insulin stimulation of Akt1 and Akt2 signaling in CF airway cells was diminished compared with that observed in airway cells expressing wild-type CFTR. These results indicate that the airway glucose barrier is regulated by insulin and is dysfunctional in CF.